ArticleOncogene2011
Phosphorylation of Crk on tyrosine 251 in the RT loop of the SH3C domain promotes Abl kinase transactivation.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- Structure-guided design of a potent peptide inhibitor targeting the interaction between CRK and ABL kinase.MedChemComm · 2018Article
- Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl.Biophysical journal · 2016Article
- Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.Nature chemical biology · 2016Article
- Reciprocal regulation of Abl kinase by Crk Y251 and Abi1 controls invasive phenotypes in glioblastoma.Oncotarget · 2015Article
- Contribution of Crk adaptor proteins to host cell and bacteria interactions.BioMed research international · 2014Review
- The adaptor protein Crk in immune response.Immunology and cell biology · 2014Review
- SH3 domains: modules of protein-protein interactions.Biophysical reviews · 2013Review
- Domain organization differences explain Bcr-Abl's preference for CrkL over CrkII.Nature chemical biology · 2012Article
- Crk and ABI1: binary molecular switches that regulate abl tyrosine kinase and signaling to the cytoskeleton.Genes & cancer · 2012Article
- Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling.Genes & cancer · 2012Article
- Models of crk adaptor proteins in cancer.Genes & cancer · 2012Article
- Activation of abl family kinases in solid tumors.Genes & cancer · 2012Article
- Article
- Functional mechanisms and roles of adaptor proteins in abl-regulated cytoskeletal actin dynamics.Journal of signal transduction · 2012Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Here, we report the identification and characterization of a novel tyrosine phosphorylation site in the carboxy-terminal Src Homology 3 (SH3) (SH3C) domain of the Crk adaptor protein. Y251 is located in the highly conserved RT loop structure of the SH3C, a region of Crk involved in the allosteric regulation of the Abl kinase. Exploiting kinase assays to show that Y251 is phosphorylated by Abl in vitro, we generated affinity-purified antisera against phosphorylated Y251 in Crk and showed that Abl induces phosphorylation at Y251 in vivo, and that the kinetics of phosphorylation at Y251 and the negative regulatory Y221 site in vitro are similar. Y251 on endogenous Crk was robustly phosphorylated in chronic myelogenous leukemia cell lines and in A431 and MDA-MB-468 cells stimulated with epidermal growth factor. Using streptavidin-biotin pull downs and unbiased high-throughput Src Homology 2 (SH2) profiling approaches, we found that a pY251 phosphopeptide binds specifically to a subset of SH2 domains, including Abl and Arg SH2, and that binding of pY251 to Abl SH2 induces transactivation of Abl 1b. Finally, the Y251F Crk mutant significantly abrogates Abl transactivation in vitro and in vivo. These studies point to a yet unrealized positive regulatory role resulting from tyrosine phosphorylation of Crk, and identify a novel mechanism by which an adaptor protein activates a non-receptor tyrosine kinase by SH2 domain displacement.
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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.