Interaction between the Amino-terminal SH3 Domain of CRK and Its Natural Target Proteins

Matsuda, Minoru; Ota, Satoshi; Tanimura, Ryuji; Nakamura, Haruki; Matuoka, Koozi; Takenawa, Tadaomi; Nagashima, Kazuo; Kurata, Takeshi

doi:10.1074/jbc.271.24.14468

Cited by 73 publications

(70 citation statements)

References 47 publications

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“…The SH3 domains have been shown to bind to e.g. the cytoplasmic tyrosine kinase c-Abl, the adaptor molecule DOCK180, and the guanine nucleotide exchange factor C3G and Sos (Feller et al, 1994;Hasegawa et al, 1996;Knudsen et al, 1995;Matsuda et al, 1996;Reedquist et al, 1996;Tanaka et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

et al. 1998

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Tyr-762 is an autophosphorylation site in the human platelet-derived growth factor (PDGF) a-receptor. In order to investigate whether phosphorylated Tyr-762 serves as a docking site for downstream signal transduction molecules, a nity puri®cation using an immobilized synthetic peptide containing phosphorylated Tyr-762 and its surrounding amino acid residues was performed. Proteins in HeLa cell lysate of molecular sizes 27, 38 and 40 kDa bound to the phosphorylated, but not to the unphosphorylated peptide. Analyses of partial amino acid sequences of the puri®ed proteins indicated that they were identical to CrkI, CrkII and CrkL respectively. The wild-type PDGF a-receptor, when expressed in porcine aortic endothelial cells, formed complexes with CrkII and CrkL upon ligand stimulation, which was speci®cally inhibited by a synthetic peptide containing phosphorylated Tyr-762. Replacement of Tyr-762 with a phenylalanine residue in the PDGF a-receptor abrogated ligand-induced binding of Crk proteins. Tyrosine phosphorylation of CrkII and CrkL increased by 1.8-and 1.3-fold, respectively, upon ligand stimulation of the wild-type areceptor. In contrast, the Y762F mutant PDGF areceptor failed to induce tyrosine phosphorylation of Crk proteins. CrkII and CrkL constitutively formed complex with the guanine nucleotide exchange factor C3G, in unstimulated as well as PDGF-stimulated cells. Moreover, the activated wild-type PDGF a-receptor but not the Y762F mutant receptor was found in a C3G immunoprecipitate, suggesting that a ternary complex between the activated PDGF a-receptor, Crk and C3G was formed. DNA synthesis stimulated by PDGF-BB as well as PDGF-induced MAP kinase activation was similar in cells expressing wild-type and mutant receptors. Interestingly, the activated PDGF b-receptor was found not to bind Crk proteins. Instead, Tyr-771 of the b-receptor, which is localized at an analogous position to Tyr-762 in the a-receptor, binds RasGAP. RasGAP is not bound to the a-receptor.

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Section: Discussionmentioning

confidence: 99%

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

et al. 1998

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“…In addition, substrates of the FAK/Src bipartite kinase complex have been identi®ed as regulators of migration (Cary et al, 1998;Klemke et al, 1998;Petit et al, 2000). Speci®cally, FAK/Srcmediated phosphorylation of Cas or paxillin creates binding sites for the adapter protein Crk (Hamasaki et al, 1996;Harte et al, 1996;Schaller and Parsons, 1995;Tachibana et al, 1997), which binds to DOCK180 (Kiyokawa et al, 1998b;Matsuda et al, 1996;Posern et al, 1998), an activator of Rac (Kiyokawa et al, 1998a;Nolan et al, 1998), thereby directing Rac activity to sites of integrin engagement with the ECM to stimulate membrane ru ing and cell migration (Cheresh et al, 1999;Hasegawa et al, 1996;Reddien and Horvitz, 2000;Wu and Horvitz, 1998). Indeed, Cas over expression in FG carcinoma cells and Chinese hamster ovary cells stimulates motility (Cary et al, 1998;Klemke et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells

et al. 2001

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Focal adhesion kinase (FAK) has been implicated in the regulation of cell migration. In addition, FAK expression is increased in a number of highly metastatic tumor cell lines. Therefore, we investigated the role of FAK in regulating migration of prostate carcinoma cell lines with increasing metastatic potential. We show that highly tumorigenic PC3 and DU145 cells exhibit intrinsic migratory capacity, while poorly tumorigenic LNCaP cells require a stimulus to migrate. Increased metastatic potential of PC3 and DU145 cells correlates with increased FAK expression, overall tyrosine phosphorylation and activity, as measured by autophosphorylation of tyrosine 397. However, in PC3 and DU145 cells, FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine phosphorylation, tyrosine 861, a Src speci®c site, is uncoupled from adhesion-dependent signaling events. Finally, inhibiting the FAK/Src signal transduction pathway by over expressing FRNK (Focal adhesion kinase-Related Non-Kinase), an inhibitor of FAK activation, or treatment with PP2, a Src family kinase inhibitor, signi®cantly inhibited migration of prostate carcinoma cell lines, demonstrating that tumor cell migration continues to be dependent on signals emanating from this pathway.

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“…For example, binding constants for Src and FAKP in the Src activation module were estimated with rate constants for Src SH2 domain binding to the pYEEI peptide, which is similar to the autophosphorylation site for FAK [35,36]. Most binding events in this pathway involve SH2 -phosphotyrosine and SH3 -PXXP binding [37,38].…”

Section: Model Parametersmentioning

confidence: 99%

Integrin-mediated signalling through the MAP-kinase pathway

2008

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The mitogen activated protein (MAP) kinase cascade, leading to extracellular-regulated kinase (ERK) activation, is a key regulator of cell growth and proliferation. The effects of ERK are mediated by differences in ERK signalling dynamics, including magnitude and duration. In vivo, ERK signalling is stimulated by both growth factors and adhesion signals. A model for adhesionmediated ERK activation is presented. Outputs of the model such as ERK and FAK activation, as well as responses to different ligand densities, are compared with published experimental data. The model then serves as a basis for understanding how adhesion may contribute to ERK signalling through changes in the dynamics of focal adhesion kinase activation. The main parameters influencing ERK are determined through screening analyses and parameter variation. With these parameters, key points in the pathway that give rise to changes in downstream signalling dynamics are identified. In particular, oncogenic Raf and Ras promote cell growth by increasing the magnitude and duration, respectively, of ERK activity. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the University of Pennsylvania's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.This journal article is available at ScholarlyCommons: http://repository.upenn.edu/be_papers/104Integrin-mediated signalling through the MAP-kinase pathway K.L. Yee, V.M. Weaver and D.A. HammerAbstract: The mitogen activated protein (MAP) kinase cascade, leading to extracellular-regulated kinase (ERK) activation, is a key regulator of cell growth and proliferation. The effects of ERK are mediated by differences in ERK signalling dynamics, including magnitude and duration. In vivo, ERK signalling is stimulated by both growth factors and adhesion signals. A model for adhesionmediated ERK activation is presented. Outputs of the model such as ERK and FAK activation, as well as responses to different ligand densities, are compared with published experimental data. The model then serves as a basis for understanding how adhesion may contribute to ERK signalling through changes in the dynamics of focal adhesion kinase activation. The main parameters influencing ERK are determined through screening analyses and parameter variation. With these parameters, key points in the pathway that give rise to changes in downstream signalling dynamics are identified. In particular, oncogenic Raf and Ras promote cell growth by increasing the magnitude and duration, respectively, of ERK activity.

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Interaction between the Amino-terminal SH3 Domain of CRK and Its Natural Target Proteins

Cited by 73 publications

References 47 publications

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells

Integrin-mediated signalling through the MAP-kinase pathway

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