Country,
Year
Summary of outcomes.
Author and Reference | Outcomes | Specific Outcome | Quality |
---|---|---|---|
HYE-JIN KIM [ ] | Accident | Fair | |
Yeon-Jin Kim [ ] | Depression and anxiety | Fair | |
DEOKJONG LEE [ ] | Gray matter abnormalities | Fair | |
JeonHyeong Lee [ ] | Musculoskeletal problems | Fair | |
Kyung Eun Lee [ ] | Anxiety | Fair | |
Yeon-Seop Lee [ ] | Carpal tunnel syndrome | Poor | |
Mi Jung Rho [ ] | Mental health problems were related to problematic smartphone use: (1) self-control (66%), (2) anxiety (25%), (3) depression (7%), and (4) dysfunctional impulsivities (3%) | Psychiatric symptoms | Fair |
Aljohara A. Alhassan [ ] | Factors associated with higher depression scores were high school-educated users (β = −2.03, adj. = 0.01) compared to the university educated group and users with higher smart phone addiction scores (β = 0.194, adj. < 0.001). | Depression | Fair |
Alosaimi, F. D. [ ] | Risk of sedentary behavior | Fair | |
Dalia El-Sayed [ ] | Depression and trait anxiety | Good | |
Jon D. Elhai [ ] | Anxiety | Good | |
Yuanming Hu [ ] | Lower white matter integrity | Fair | |
Jon D. Elhai [ ] | COVID-19 anxiety | Good | |
Linbo Zhuang [ ] | cervical disc degeneration | Good | |
Yasemin P. Demir [ ] | less than 0.05); a strong positive correlation between MPPUS and ESS (r = 0.675, less than 0.05); and a negative correlation between MPPUS and 24-h MQoLQ (r = −0.508, less than 0.05) | Increased headache duration, poor sleep quality | Fair |
KADİR DEMİRCİ [ ] | Depression, anxiety, and daytime dysfunction | Fair | |
Ayse Gokce [ ] | Increased smoking | Fair | |
Betul Ozcan [ ] | Poor sleep quality | Good | |
S HariPriya [ ] | Poor sleep quality, less physical activity | Good | |
Hsien-Yuan Lane [ ] | Psychological distress, poor sleep quality | Good | |
Anna Maria [ ] | Social anxiety | Fair | |
Jon D. Elhai [ ] | Worry and anger | Good | |
Matteo Megna [ ] | Psoriatic arthritis | Fair | |
Arunrat TangmunkongvorakulI [ ] | < 0.001) | Psychological well-being | Fair |
Zaheer Hussain [ ] | Anxiety | Good | |
MILES RICHARDSON [ ] | Connectedness with nature and anxiety | Fair | |
Asem A. Alageel [ ] | Insomnia, depression, adult ADHD | Fair |
3.2.1. mental health.
As outlined in Table 2 , mental health was associated with SA in fourteen studies [ 22 , 25 , 27 , 28 , 30 , 31 , 33 , 36 , 40 , 41 , 42 , 45 , 46 , 47 ]. Depression and anxiety were the most common mental health conditions associated with SA [ 22 , 25 , 28 , 30 , 31 , 33 , 36 , 41 , 45 , 47 ]. Several depression measures were used; however, the Beck Depression Inventory was the most common measure used [ 28 , 30 , 36 , 40 ]. Alhassan et al. (2018) revealed that less-educated people and young adult users of the smartphone were at high risk of depression. Another study [ 28 ] found that the groups who were classified as smartphone-addicted had an increased risk of depression (relative risk 1.337; p < 0.001) and anxiety (relative risk 1.402; p < 0.001) [ 28 ]. Miles Richardson et al. (2018) found that problematic smartphone use (PSU) was positively related to anxiety [ 46 ].
Social anxiety was also associated with SA [ 41 ]. For instance, a study conducted in China during COVID-19 reported that COVID-19 anxiety was associated with the severity of problematic smartphone use [ 33 ].
Interestingly, female participants were more susceptible to SA [ 36 ] and showed significantly higher dependence on smartphones than men [ 25 ]. Further, a study conducted among university students in Thailand demonstrated that not only were female students more likely to be smartphone addicted, but smartphone addiction among female participants was likely to be negatively associated with psychological well-being [ 44 ].
Musculoskeletal problems.
The effect of SA on the musculoskeletal system was identified in four studies [ 24 , 26 , 34 , 43 ] ( Table 2 ). Among those studies, two studies reported cervical problems [ 24 , 34 ], one study demonstrated nerve thickness [ 26 ], and one study showed psoriatic arthritis [ 43 ]. Lee et al. (2014) compared cervical spine repositioning errors in different smartphone addiction groups and revealed that there were significant differences between non-addicted, moderately addicted, and severely addicted groups; the severe smartphone addict group showed the largest changes in posture, the cervical repositioning errors of flexion (3.2 ± 0.8), extension (4.9 ± 1.1), right lateral flexion (3.9 ± 1.0), and left lateral flexion (4.1 ± 0.7). [ 24 ]. A study conducted among 2438 young patients suffering from chronic neck pain found that cervical disc degeneration was more likely to be associated with SA [ 34 ]. Another study conducted among university students revealed that excess smartphone use can cause nerve injury [ 26 ]. Megna et al. (2018) found that SA was linked to higher signs of inflammation in the musculoskeletal structures of hand joints.
Five studies showed an association between smartphone addiction and sleep quality [ 29 , 35 , 38 , 39 , 40 ]. The Pittsburgh Sleep Quality Index (PSQI) was used in all five studies ( Table 1 ). A study conducted by Fahad et al. (2016) among 2367 university students reported 43% of the participants had decreased their sleeping hours due to SA, and 30% of the participants had an unhealthy lifestyle including weight gain, reduced exercise, and the consumption of more fast food when diagnosed with SA [ 29 ]. Another study conducted among migraine patients reported that SA can increase headache duration and decrease sleep quality [ 35 ].
One study conducted by Hye-Jin Kim et al. (2017) revealed that SA is associated with different types of accidents, such as traffic accidents; falls/slips; bumps/collisions; being trapped in the subway, impalement, cuts, and exit wounds; and burns or electric shocks [ 21 ]. The study found that self-reported experience of accidents was significantly associated with SA [ 21 ].
Two studies reported the neurological effect of SA [ 23 , 32 ]; one study found alterations in white matter integrity [ 32 ] and another study reported smaller grey matter volume [ 23 ]. Hu et al. (2017) used a high-resolution magnetic resonance imaging technique to identify white matter integrity in young adults with SA and found that smartphone-addicted participants had significantly lower white matter integrity [ 32 ]. Lee et al. (2019) found that smartphone-addicted participants had significantly smaller grey matter volume (GMV) in the right lateral orbitofrontal cortex (OFC) [ 23 ].
In recent years, several articles have examined the role of smartphone addiction and associated health outcomes among the adult population, however, substantial gaps still remain. To the best of our knowledge, no previous systematic review has been conducted to summarize these findings among this cohort. Our review is the first systematic review that utilizes empirical evidence from the last decades that demonstrates the relationship between smartphone addiction and health outcomes among adults. Interestingly, studies conducted in different parts of the world showed similar effects on health outcomes as a result of smartphone addiction. Hence, the consistency across the studies strengthens the study findings, emphasizing the association between SA and health outcomes.
Our findings suggest that depression and anxiety are significantly linked with smartphone addiction. One national USA survey found that 46% of smartphone owners believed they could not live without their phones [ 48 ]. Overuse patterns of smartphones involves a tendency to check notifications all the time, and such behavior patterns can induce “reassurance seeking” which broadly includes symptoms such as depression and anxiety [ 49 ]. This “reassurance seeking” pathway corresponds to those individuals whose smartphone use is driven by the necessity to maintain relationships and obtain reassurance from others. Bilieux and colleagues explained this reassurance-seeking behavior with the theoretical model of “problematic mobile phone use” [ 50 ]. In addition, this checking behavior is related to the next pathway, the “fear of missing out” (FOMO). One study found that FOMO mediated relations between both depression and anxiety severity with SA [ 51 ].
From our results, it is evident that musculoskeletal pain and insomnia are the two most common physical problems related to SA. Fingers, cervical, back, and shoulder problems are most commonly linked to excessive smartphone usage. Prolonged use of smartphones can cause defective postures such as forwarding head posture, which can produce injuries to the cervical spine and cause cervical pain [ 52 ]. Numerous studies found De Quervain tenosynovitis (characterized by pain in the wrist over the radio styloid process—the thumb side of wrist) was associated with different electronic devices like gaming controllers, tablets, and smartphones [ 53 , 54 ]. Texting and chatting through smartphones have been considered a risk factor for De Quervain tenosynovitis [ 55 ].
Poor sleep quality and difficulty in falling asleep or maintaining sleep has been identified as one of the negative consequences of SA, which is similar to our results [ 56 , 57 ]. Moreover, in line with our finding, another systematic review revealed that SA is related to poorer sleep quality [ 58 ]. One study found that 75% of the young adults (age < 30 years) take their phones to bed, which may increase the likelihood of poor sleep quality [ 59 ]. Smartphone addicts are unsuccessful at controlling their smartphone use, even in bed. Again, fear of missing out could be the reason of taking phones in the beds as they do not want to miss any notification [ 60 , 61 ]. In addition, blue light emitted by smartphones can have a negative effect on circadian rhythms, leading to negative sleep consequences, such as going to sleep later than intended and thus reducing overall sleep time [ 62 ].
The neurological effect of SA is not clear yet from this review. However, currently neuroimaging studies play an important role in understanding the complexity of addictive behavior [ 63 ], as they can assess any pathological change in the brain. Two studies in this review reported the negative changes in grey matter and white matter integrity in the brain with the assistance of neuroimaging ( Table 2 ), which is similar to the neuropathy caused by substance abuse [ 64 , 65 ] and Internet addiction [ 66 , 67 ]. However, the modest sample size and the lack of a clinical evaluation are the potential limitations of these studies [ 23 , 32 ].
This review indicates that smartphone addiction shares similar features with substance abuse. A consistent relationship has been demonstrated between SA and physical and mental health symptoms, including depression, anxiety, musculoskeletal problems, and poor sleep. However, smartphones have become a part of daily life, facilitating work, education, or entertainment. Therefore, it is important not only to utilize the advantages of the smartphone but also to reduce the negative consequences. To address SA in a proper way, a validated definition and consistent diagnostic criteria of SA is required. The findings from this research suggest that healthcare providers and policymakers should recognize the problem and take necessary steps in raising community awareness about SA and its physical and mental impact.
This systematic review has several limitations. First, all of the selected studies were cross-sectional ( Table 1 ), therefore drawing conclusions about causal directions of associations is not possible. Secondly, all the papers were excluded if not in the English language; however, SA has received attention in Asian and European countries, and findings may have been published in other languages. This may lead to exclusion of studies conducted in diverse cultures and may bias the results of the review. Thirdly, most of the studies that were qualified to be included in this review were performed in developed countries, which may question the generalizability our findings to developing countries. Finally, most of the outcomes were reported over less than one year of follow-up. No standard scale and cut-off scores were used for the determination of smartphone addiction.
The current review describes the effect of smartphones on health outcomes in the adult population. Although the diagnostic criteria and effect of smartphone addiction are yet to be fully established, this review provides invaluable findings about the health impact of smartphone addiction and has significant implications for policy and decision makers. There is a need for more longitudinal studies to validate and strengthen this review’s findings.
The following are available online at https://www.mdpi.com/article/10.3390/ijerph182212257/s1 , Table S1. Electronic search strategy.
Z.A.R. conceptualized and designed the study, conducted initial searches, assessed the eligibility of the retrieved papers in the titles/abstracts and full text. S.B.Z. and M.S.A. independently reviewed all the retrieved abstracts and selected eligible papers. Z.A.R., A.-M.P., S.B.Z., M.S.A. and H.H. critically assessed the eligible studies and extracted data. Z.A.R. analyzed and interpreted the data and drafted the manuscript. All authors critically reviewed the manuscript. A.-M.P. and H.H. reviewed and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.
This research received no funding.
Informed consent statement, data availability statement, conflicts of interest.
Authors declared no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Numbers, Facts and Trends Shaping Your World
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Which social media platforms are most common, who uses each social media platform, find out more, social media fact sheet.
Many Americans use social media to connect with one another, engage with news content, share information and entertain themselves. Explore the patterns and trends shaping the social media landscape.
To better understand Americans’ social media use, Pew Research Center surveyed 5,733 U.S. adults from May 19 to Sept. 5, 2023. Ipsos conducted this National Public Opinion Reference Survey (NPORS) for the Center using address-based sampling and a multimode protocol that included both web and mail. This way nearly all U.S. adults have a chance of selection. The survey is weighted to be representative of the U.S. adult population by gender, race and ethnicity, education and other categories.
Polls from 2000 to 2021 were conducted via phone. For more on this mode shift, read our Q&A.
Here are the questions used for this analysis , along with responses, and its methodology .
A note on terminology: Our May-September 2023 survey was already in the field when Twitter changed its name to “X.” The terms Twitter and X are both used in this report to refer to the same platform.
YouTube and Facebook are the most-widely used online platforms. About half of U.S. adults say they use Instagram, and smaller shares use sites or apps such as TikTok, LinkedIn, Twitter (X) and BeReal.
Year | YouTube | TikTok | Snapchat | Twitter (X) | BeReal | Nextdoor | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
8/5/2012 | 54% | 9% | 10% | 16% | 13% | |||||||
8/7/2012 | 14% | |||||||||||
12/9/2012 | 11% | 13% | 13% | |||||||||
12/16/2012 | 57% | |||||||||||
5/19/2013 | 15% | |||||||||||
7/14/2013 | 16% | |||||||||||
9/16/2013 | 57% | 14% | 17% | 17% | 14% | |||||||
9/30/2013 | 16% | |||||||||||
1/26/2014 | 16% | |||||||||||
9/21/2014 | 58% | 21% | 22% | 23% | 19% | |||||||
4/12/2015 | 62% | 24% | 26% | 22% | 20% | |||||||
4/4/2016 | 68% | 28% | 26% | 25% | 21% | |||||||
1/10/2018 | 73% | 68% | 35% | 29% | 25% | 22% | 27% | 24% | ||||
2/7/2019 | 73% | 69% | 37% | 28% | 27% | 20% | 24% | 22% | 11% | |||
2/8/2021 | 81% | 69% | 40% | 31% | 21% | 28% | 23% | 25% | 23% | 18% | 13% | |
9/5/2023 | 83% | 68% | 47% | 35% | 33% | 30% | 29% | 27% | 22% | 22% | 3% |
Note: The vertical line indicates a change in mode. Polls from 2012-2021 were conducted via phone. In 2023, the poll was conducted via web and mail. For more details on this shift, please read our Q&A . Refer to the topline for more information on how question wording varied over the years. Pre-2018 data is not available for YouTube, Snapchat or WhatsApp; pre-2019 data is not available for Reddit; pre-2021 data is not available for TikTok; pre-2023 data is not available for BeReal. Respondents who did not give an answer are not shown.
Source: Surveys of U.S. adults conducted 2012-2023.
Usage of the major online platforms varies by factors such as age, gender and level of formal education.
% of U.S. adults who say they ever use __ by …
Ages 18-29 | 30-49 | 50-64 | 65+ | |
---|---|---|---|---|
67 | 75 | 69 | 58 | |
78 | 59 | 35 | 15 | |
32 | 40 | 31 | 12 | |
Twitter (X) | 42 | 27 | 17 | 6 |
45 | 40 | 33 | 21 | |
Snapchat | 65 | 30 | 13 | 4 |
YouTube | 93 | 92 | 83 | 60 |
32 | 38 | 29 | 16 | |
44 | 31 | 11 | 3 | |
TikTok | 62 | 39 | 24 | 10 |
BeReal | 12 | 3 | 1 | <1 |
Men | Women | |
---|---|---|
59 | 76 | |
39 | 54 | |
31 | 29 | |
Twitter (X) | 26 | 19 |
19 | 50 | |
Snapchat | 21 | 32 |
YouTube | 82 | 83 |
27 | 31 | |
27 | 17 | |
TikTok | 25 | 40 |
BeReal | 2 | 5 |
White | Black | Hispanic | Asian* | |
---|---|---|---|---|
69 | 64 | 66 | 67 | |
43 | 46 | 58 | 57 | |
30 | 29 | 23 | 45 | |
Twitter (X) | 20 | 23 | 25 | 37 |
36 | 28 | 32 | 30 | |
Snapchat | 25 | 25 | 35 | 25 |
YouTube | 81 | 82 | 86 | 93 |
20 | 31 | 54 | 51 | |
21 | 14 | 23 | 36 | |
TikTok | 28 | 39 | 49 | 29 |
BeReal | 3 | 1 | 4 | 9 |
Less than $30,000 | $30,000- $69,999 | $70,000- $99,999 | $100,000+ | |
---|---|---|---|---|
63 | 70 | 74 | 68 | |
37 | 46 | 49 | 54 | |
13 | 19 | 34 | 53 | |
Twitter (X) | 18 | 21 | 20 | 29 |
27 | 34 | 35 | 41 | |
Snapchat | 27 | 30 | 26 | 25 |
YouTube | 73 | 83 | 86 | 89 |
26 | 26 | 33 | 34 | |
12 | 23 | 22 | 30 | |
TikTok | 36 | 37 | 34 | 27 |
BeReal | 3 | 3 | 3 | 5 |
High school or less | Some college | College graduate+ | |
---|---|---|---|
63 | 71 | 70 | |
37 | 50 | 55 | |
10 | 28 | 53 | |
Twitter (X) | 15 | 24 | 29 |
26 | 42 | 38 | |
Snapchat | 26 | 32 | 23 |
YouTube | 74 | 85 | 89 |
25 | 23 | 39 | |
14 | 23 | 30 | |
TikTok | 35 | 38 | 26 |
BeReal | 3 | 4 | 4 |
Urban | Suburban | Rural | |
---|---|---|---|
66 | 68 | 70 | |
53 | 49 | 38 | |
31 | 36 | 18 | |
Twitter (X) | 25 | 26 | 13 |
31 | 36 | 36 | |
Snapchat | 29 | 26 | 27 |
YouTube | 85 | 85 | 77 |
38 | 30 | 20 | |
29 | 24 | 14 | |
TikTok | 36 | 31 | 33 |
BeReal | 4 | 4 | 2 |
Rep/Lean Rep | Dem/Lean Dem | |
---|---|---|
70 | 67 | |
43 | 53 | |
29 | 34 | |
Twitter (X) | 20 | 26 |
35 | 35 | |
Snapchat | 27 | 28 |
YouTube | 82 | 84 |
25 | 33 | |
20 | 25 | |
TikTok | 30 | 36 |
BeReal | 4 | 4 |
This fact sheet was compiled by Research Assistant Olivia Sidoti , with help from Research Analyst Risa Gelles-Watnick , Research Analyst Michelle Faverio , Digital Producer Sara Atske , Associate Information Graphics Designer Kaitlyn Radde and Temporary Researcher Eugenie Park .
Follow these links for more in-depth analysis of the impact of social media on American life.
Find more reports and blog posts related to internet and technology .
1615 L St. NW, Suite 800 Washington, DC 20036 USA (+1) 202-419-4300 | Main (+1) 202-857-8562 | Fax (+1) 202-419-4372 | Media Inquiries
ABOUT PEW RESEARCH CENTER Pew Research Center is a nonpartisan fact tank that informs the public about the issues, attitudes and trends shaping the world. It conducts public opinion polling, demographic research, media content analysis and other empirical social science research. Pew Research Center does not take policy positions. It is a subsidiary of The Pew Charitable Trusts .
© 2024 Pew Research Center
Key takeways/summary.
UCLA scientists have identified a protein that plays a critical role in regulating human blood stem cell self-renewal by helping them sense and interpret signals from their environment.
The study , published in Nature, brings researchers one step closer to developing methods to expand blood stem cells in a lab dish, which could make life-saving transplants of these cells more available and increase the safety of blood stem cell-based treatments, such as gene therapies.
Blood stem cells, also known as hematopoietic stem cells, have the ability to make copies of themselves via a process called self-renewal, and can differentiate to produce all the blood and immune cells found in the body. For decades, transplants of these cells have been used as life-saving treatments for blood cancers such as leukemia and various other blood and immune disorders.
However, blood stem cell transplants have significant limitations. Finding a compatible donor can be difficult, particularly for people of non-European ancestry, and the number of stem cells available for transplant can be too low to safely treat a person’s disease.
These limitations persist because blood stem cells that have been removed from the body and placed in a lab dish quickly lose their ability to self-renew. After decades of research, scientists have come achingly close to solving this problem.
“We’ve figured out how to produce cells that look just like blood stem cells and have all of their hallmarks, but when these cells are used in transplants, many of them still don’t work; there’s something missing,” said Dr. Hanna Mikkola , senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
To pinpoint the missing piece that prevents these blood stem cell-like cells from being fully functional, Julia Aguade Gorgorio, the paper’s first and co-corresponding author, analyzed sequencing data to identify genes that are silenced when blood stem cells are placed in a lab dish. One such gene, MYCT1, which encodes a protein by the same name, stood out as being essential to these cells’ self-renewal capacity.
They found that MYCT1 regulates a process called endocytosis, which plays a key role in how blood stem cells take in the signals from their environment that tell them when to self-renew, when to differentiate and when to be quiet.
“When cells perceive a signal, they have to internalize it and process it; MYCT1 controls how fast and how efficiently blood stem cells perceive these signals,” said Aguade Gorgorio, an assistant project scientist in the Mikkola lab. “Without this protein, the signals from the cells’ environment turn from whispers into screams and the cells become stressed out and dysregulated.”
The researchers compare MYCT1 to the sensors in modern cars that monitor all nearby activity and selectively relay the most crucial information to drivers at the right time, aiding decisions like when to safely turn or change lanes. Without MYCT1, blood stem cells resemble anxious drivers who, used to relying on these sensors, suddenly find themselves lost without their guidance.
Next, the researchers used a viral vector to reintroduce MYCT1 to see if its presence could restore blood stem cell self-renewal in a lab dish. Restoration of MYCT1, they found, not only made the blood stem cells less stressed and enabled them to self-renew in culture but also allowed these expanded cells to function effectively after being transplanted into mouse models.
As a next step, the team will investigate why the silencing of the MYCT1 gene occurs, and then, how to prevent this silencing without the use of a viral vector, which would be safer for use in a clinical setting.
“If we can find a way to maintain MYCT1 expression in blood stem cells in culture and after transplant, it will open the door to maximize all these other remarkable advances in the field,” said Mikkola, who is a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Health Jonsson Comprehensive Cancer Center . “This would not only make blood stem cell transplants more accessible and effective but also improve the safety and affordability of gene therapies that utilize these cells.”
This work was supported by the National Institutes of Health, the Swiss National Science Foundation, the European Molecular Biology Organization, the UCLA Jonsson Cancer Center Foundation, the James B. Pendleton Charitable Trust, the McCarthy Family Foundation, the California Institute for Regenerative Medicine, the UCLA AIDS Institute, the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center, the Royal Society, the Wellcome Trust and the UCLA Broad Stem Cell Research Center Stem Cell Training Program.
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A newly complete database of human protein kinases and their preferred binding sites provides a powerful new platform to investigate cell signaling pathways.
Culminating 25 years of research, MIT, Harvard University, and Yale University scientists and collaborators have unveiled a comprehensive atlas of human tyrosine kinases — enzymes that regulate a wide variety of cellular activities — and their binding sites.
The addition of tyrosine kinases to a previously published dataset from the same group now completes a free, publicly available atlas of all human kinases and their specific binding sites on proteins, which together orchestrate fundamental cell processes such as growth, cell division, and metabolism.
Now, researchers can use data from mass spectrometry, a common laboratory technique, to identify the kinases involved in normal and dysregulated cell signaling in human tissue, such as during inflammation or cancer progression.
“I am most excited about being able to apply this to individual patients’ tumors and learn about the signaling states of cancer and heterogeneity of that signaling,” says Michael Yaffe, who is the David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the new study. “This could reveal new druggable targets or novel combination therapies.”
The study, published in Nature , is the product of a long-standing collaboration with senior authors Lewis Cantley at Harvard Medical School and Dana-Farber Cancer Institute, Benjamin Turk at Yale School of Medicine, and Jared Johnson at Weill Cornell Medical College.
The paper’s lead authors are Tomer Yaron-Barir at Columbia University Irving Medical Center, and MIT’s Brian Joughin, with contributions from Kontstantin Krismer, Mina Takegami, and Pau Creixell.
Kinase kingdom
Human cells are governed by a network of diverse protein kinases that alter the properties of other proteins by adding or removing chemical compounds called phosphate groups. Phosphate groups are small but powerful: When attached to proteins, they can turn proteins on or off, or even dramatically change their function. Identifying which of the almost 400 human kinases phosphorylate a specific protein at a particular site on the protein was traditionally a lengthy, laborious process.
Beginning in the mid 1990s, the Cantley laboratory developed a method using a library of small peptides to identify the optimal amino acid sequence — called a motif, similar to a scannable barcode — that a kinase targets on its substrate proteins for the addition of a phosphate group. Over the ensuing years, Yaffe, Turk, and Johnson, all of whom spent time as postdocs in the Cantley lab, made seminal advancements in the technique, increasing its throughput, accuracy, and utility.
Johnson led a massive experimental effort exposing batches of kinases to these peptide libraries and observed which kinases phosphorylated which subsets of peptides. In a corresponding Nature paper published in January 2023, the team mapped more than 300 serine/threonine kinases, the other main type of protein kinase, to their motifs. In the current paper, they complete the human “kinome” by successfully mapping 93 tyrosine kinases to their corresponding motifs.
Next, by creating and using advanced computational tools, Yaron-Barir, Krismer, Joughin, Takegami, and Yaffe tested whether the results were predictive of real proteins, and whether the results might reveal unknown signaling events in normal and cancer cells. By analyzing phosphoproteomic data from mass spectrometry to reveal phosphorylation patterns in cells, their atlas accurately predicted tyrosine kinase activity in previously studied cell signaling pathways.
For example, using recently published phosphoproteomic data of human lung cancer cells treated with two targeted drugs, the atlas identified that treatment with erlotinib, a known inhibitor of the protein EGFR, downregulated sites matching a motif for EGFR. Treatment with afatinib, a known HER2 inhibitor, downregulated sites matching the HER2 motif. Unexpectedly, afatinib treatment also upregulated the motif for the tyrosine kinase MET, a finding that helps explain patient data linking MET activity to afatinib drug resistance.
Actionable results
There are two key ways researchers can use the new atlas. First, for a protein of interest that is being phosphorylated, the atlas can be used to narrow down hundreds of kinases to a short list of candidates likely to be involved. “The predictions that come from using this will still need to be validated experimentally, but it’s a huge step forward in making clear predictions that can be tested,” says Yaffe.
Second, the atlas makes phosphoproteomic data more useful and actionable. In the past, researchers might gather phosphoproteomic data from a tissue sample, but it was difficult to know what that data was saying or how to best use it to guide next steps in research. Now, that data can be used to predict which kinases are upregulated or downregulated and therefore which cellular signaling pathways are active or not.
“We now have a new tool now to interpret those large datasets, a Rosetta Stone for phosphoproteomics,” says Yaffe. “It is going to be particularly helpful for turning this type of disease data into actionable items.”
In the context of cancer, phosophoproteomic data from a patient’s tumor biopsy could be used to help doctors quickly identify which kinases and cell signaling pathways are involved in cancer expansion or drug resistance, then use that knowledge to target those pathways with appropriate drug therapy or combination therapy.
Yaffe’s lab and their colleagues at the National Institutes of Health are now using the atlas to seek out new insights into difficult cancers, including appendiceal cancer and neuroendocrine tumors. While many cancers have been shown to have a strong genetic component, such as the genes BRCA1 and BRCA2 in breast cancer, other cancers are not associated with any known genetic cause. “We’re using this atlas to interrogate these tumors that don’t seem to have a clear genetic driver to see if we can identify kinases that are driving cancer progression,” he says.
Biological insights
In addition to completing the human kinase atlas, the team made two biological discoveries in their recent study. First, they identified three main classes of phosphorylation motifs, or barcodes, for tyrosine kinases. The first class is motifs that map to multiple kinases, suggesting that numerous signaling pathways converge to phosphorylate a protein boasting that motif. The second class is motifs with a one-to-one match between motif and kinase, in which only a specific kinase will activate a protein with that motif. This came as a partial surprise, as tyrosine kinases have been thought to have minimal specificity by some in the field.
The final class includes motifs for which there is no clear match to one of the 78 classical tyrosine kinases. This class includes motifs that match to 15 atypical tyrosine kinases known to also phosphorylate serine or threonine residues. “This means that there’s a subset of kinases that we didn’t recognize that are actually playing an important role,” says Yaffe. It also indicates there may be other mechanisms besides motifs alone that affect how a kinase interacts with a protein.
The team also discovered that tyrosine kinase motifs are tightly conserved between humans and the worm species C. elegans, despite the species being separated by more than 600 million years of evolution. In other words, a worm kinase and its human homologue are phosphorylating essentially the same motif. That sequence preservation suggests that tyrosine kinases are highly critical to signaling pathways in all multicellular organisms, and any small change would be harmful to an organism.
The research was funded by the Charles and Marjorie Holloway Foundation, the MIT Center for Precision Cancer Medicine, the Koch Institute Frontier Research Program via L. Scott Ritterbush, the Leukemia and Lymphoma Society, the National Institutes of Health, Cancer Research UK, the Brain Tumour Charity, and the Koch Institute Support (core) grant from the National Cancer Institute.
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1. Introduction. In 2018, approximately 77 percent of America's inhabitants owned a smartphone (Pew Research Center, 2018), defined here as a mobile phone that performs many of the functions of a computer (Alosaimi, Alyahya, Alshahwan, Al Mahyijari, & Shaik, 2016).In addition, a survey conducted in 2015 showed that 46 percent of Americans reported that they could not live without their ...
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mobile phones in the classroom and 45% of the respondents were supportive. The researchers. explained that the more American adults are used to their devices in their everyday life, the. more ...
In contrast to current educators, 45% supported the use of mobile phones in the classroom (while 25% did not), compared to earlier research that found only one-fourth of the preservice teachers supported their use. More than half of the preservice teachers (58%) indicated that mobile phones support student learning, whereas far fewer (21% ...
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presence of a cell phone can affect cognitive functioning (Wilmer, Sherman & Chein, 2017), and. ... 2.2 Current research on the impact of mobile technology and social media platforms.
According to recent surveys, 75% of the world's population owns a cell phone. 6,7 Surveys in 2019 indicated that there were 5.11 billion unique mobile phone users, and that 2.71 billion of them used smartphones. People from China (> 782 million users) and India (> 386 million users) are the largest consumers of smartphones, followed by the ...
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the risk of being addicted to their phones. There are some medical concerns that have been raised in association with the use of smartphones; there also happens to be effects such as insomnia, anxiety, misery and others (Ezemenaka, 2013). All these effects usually develop when students find themselves without their cell phones. Ebiye (2015)
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Mission. The Purdue On-Campus Writing Lab and Purdue Online Writing Lab assist clients in their development as writers—no matter what their skill level—with on-campus consultations, online participation, and community engagement. The Purdue Writing Lab serves the Purdue, West Lafayette, campus and coordinates with local literacy initiatives.
1. Introduction. The 21st century is known as the age of information technology. Wireless communication and the internet are remarkable entities resulting in revolutionary changes in the field of communication [].In 2007, computer-based phones (smartphones) were introduced [].Since then, smartphones have become an indispensable part of daily life in all communities and countries.
Updated: May 23, 2024. |. Beyond AT&T, Verizon, and T-Mobile, there are now dozens of smaller 5G cellular service providers across the U.S. Each offers a handful of prepaid or postpaid, contract ...
To better understand Americans' social media use, Pew Research Center surveyed 5,733 U.S. adults from May 19 to Sept. 5, 2023. Ipsos conducted this National Public Opinion Reference Survey (NPORS) for the Center using address-based sampling and a multimode protocol that included both web and mail.
Our team of tech experts spent over 300 hours of research, online shopping, conversations with customer service, and hands-on testing to choose our picks for the best cell phones for seniors.
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The findings could help make blood stem cell transplants available to more people and improve the accessibility and safety of gene therapies that use these cells. UCLA scientists have identified a protein that plays a critical role in regulating human blood stem cell self-renewal by helping them sense and interpret signals from their environment.
New Cisco ThousandEyes capabilities and AI-native workflows in Cisco Networking Cloud will deliver Digital Experience Assurance, transforming IT operations. Cisco is a worldwide technology leader. Our purpose is to power an inclusive future for all through software, networking, security, computing, and more solutions.
Culminating 25 years of research, MIT, Harvard University, and Yale University scientists and collaborators have unveiled a comprehensive atlas of human tyrosine kinases — enzymes that regulate a wide variety of cellular activities — and their binding sites. ... The paper's lead authors are Tomer Yaron-Barir at Columbia University Irving ...