ArticleMolecular and cellular biology2013
Activation of extracellular signal-regulated kinase but not of p38 mitogen-activated protein kinase pathways in lymphocytes requires allosteric activation of SOS.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Rasgrp1-Mediated Dampening of EGFR Signals Supports Coordinated Mammary Gland Development.Cells · 2026Article
- Regulatory roles of MicroRNA in shaping T cell function, differentiation and polarization.Seminars in cell & developmental biology · 2022Review
- Article
- Alternative ZAP70-p38 signals prime a classical p38 pathway through LAT and SOS to support regulatory T cell differentiation.Science signaling · 2019Article
- Multiple sources of signal amplification within the B-cell Ras/MAPK pathway.Molecular biology of the cell · 2019Article
- The Interdependent Activation of Son-of-Sevenless and Ras.Cold Spring Harbor perspectives in medicine · 2019Review
- Understanding the Dynamics of T-Cell Activation in Health and Disease Through the Lens of Computational Modeling.JCO clinical cancer informatics · 2019Review
- Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.Nature communications · 2017Article
- One-way membrane trafficking of SOS in receptor-triggered Ras activation.Nature structural & molecular biology · 2016Article
- Article
- Monitoring the Waiting Time Sequence of Single Ras GTPase Activation Events Using Liposome Functionalized Zero-Mode Waveguides.Nano letters · 2016Article
- EGF receptor uses SOS1 to drive constitutive activation of NFκB in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.Frontiers in immunology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.