Abstract
Abstract. Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a “molecular switch” for the induction of cell migration and appears to contribute to the invasive property of tumors.
References
43
Referenced
550
10.1016/0092-8674(93)90296-3
/ Cell / SH3 domains direct cellular localization of signaling molecules by Bar-Sagi (1993)10.1016/S0021-9258(19)50057-6
/ J Biol Chem / Tyrosine-phosphorylated epidermal growth factor receptor and cellular p130 provide high affinity binding substrates to analyze Crk-phosphotyrosine-dependent interactions in vitro by Birge (1992)10.1172/JCI119298
/ J Clin Invest / Insulin-like growth factor receptor cooperates with integrin αvβ5 to promote tumor cell dissemination in vivo by Brooks (1997)10.1242/jcs.109.7.1787
/ J Cell Sci / Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn by Cary (1996)10.1083/jcb.127.3.847
/ J Cell Biol / Epidermal growth factor receptor–mediated cell motility: phospholipase C activity is required but mitogen-activated protein kinase is not sufficient for induced cell movement by Chen (1994){'key': '2023072823032213400_B6', 'first-page': '1407', 'article-title': 'Transient functional expression of αvβ3 on vascular cells during wound repair', 'volume': '148', 'author': 'Clark', 'year': '1996', 'journal-title': 'Am J Pathol'}
/ Am J Pathol / Transient functional expression of αvβ3 on vascular cells during wound repair by Clark (1996)10.1016/0968-0004(94)90129-5
/ Trends Biochem Sci / SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl by Feller (1994)10.1002/j.1460-2075.1994.tb06518.x
/ EMBO (Eur Mol Biol Organ) J / C-Abl kinase regulates the protein binding activity of c-Crk by Feller (1994){'key': '2023072823032213400_B9', 'first-page': '1465', 'article-title': 'Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways', 'volume': '10', 'author': 'Feller', 'year': '1995', 'journal-title': 'Oncogene'}
/ Oncogene / Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways by Feller (1995)10.1128/MCB.16.11.6408
/ Mol Cell Biol / Identification of p130CAS as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST by Garton (1996)10.1091/mbc.7.8.1209
/ Mol Biol Cell / Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation by Gilmore (1996){'key': '2023072823032213400_B12', 'first-page': '1443', 'article-title': 'A role for Ras in v-Crk transformation', 'volume': '7', 'author': 'Greulich', 'year': '1996', 'journal-title': 'Cell Growth Diff'}
/ Cell Growth Diff / A role for Ras in v-Crk transformation by Greulich (1996)10.1002/bies.950190208
/ BioEssays / Signaling through focal adhesion kinase by Hanks (1997)10.1074/jbc.271.23.13649
/ J Biol Chem / p130CAS, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase by Harte (1996)10.1128/MCB.16.4.1770
/ Mol Cell Biol / DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane by Hasegawa (1996)10.1083/jcb.131.6.1857
/ J Cell Biol / The assembly of integrin complexes requires both extracellular matrix and intracellular rho/rac GTPases by Hotchin (1995)10.1083/jcb.134.6.1551
/ J Cell Biol / Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity by Huttenlocher (1996)10.1038/377539a0
/ Nature / Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice by Ilic (1995)10.1083/jcb.127.3.859
/ J Cell Biol / Receptor tyrosine kinase signaling required for integrin αvβ5-directed cell motility but not adhesion on vitronectin by Klemke (1994)10.1083/jcb.137.2.481
/ J Cell Biol / Regulation of cell motility by mitogen-activated protein kinase by Klemke (1997)10.1016/0898-6568(96)00067-8
/ Cell Signalling / Emerging components of the Crk oncogene product: the first identified adaptor protein by Matsuda (1996)10.1016/S0021-9258(18)53628-0
/ J Biol Chem / Structural requirement of CRK SH2 region for binding to phosphotyrosine-containing proteins by Matsuda (1993){'key': '2023072823032213400_B23', 'first-page': '5495', 'article-title': 'CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of ras in PC12 cells', 'volume': '14', 'author': 'Matsuda', 'year': '1994', 'journal-title': 'Mol Cell Biol'}
/ Mol Cell Biol / CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of ras in PC12 cells by Matsuda (1994)10.1016/S0960-9822(95)00060-1
/ Curr Biol / Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases by Mayer (1995)10.1038/375338a0
/ Nature / A role for Rac in Tiam1-induced membrane ruffling and invasion by Michiels (1995)10.1016/S0092-8674(05)80019-4
/ Cell / Selective activation of the JNK signaling cascade and c-jun transcriptional activity by the small GTPases Rac and Cdc42HS by Minden (1995)10.1128/MCB.17.7.3884
/ Mol Cell Biol / Requirements for localization of p130CAS to focal adhesions by Nakamoto (1997)10.1172/JCI116007
/ J Clin Invest / Human melanoma cells derived from lymphatic metastasis use integrin αvβ3 to adhere to lymph node vitronectin by Nip (1992)10.1074/jbc.270.25.15398
/ J Biol Chem / Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs by Nojima (1995)10.1038/385537a0
/ Nature / Integrin-ligand binding properties govern speed through cell-substratum adhesiveness by Palecek (1997)10.1016/S0955-0674(96)80059-7
/ Curr Opin Cell Biol / Integrin-mediated signaling: regulation by protein tyrosine kinases and small GTP-binding proteins by Parsons (1996)10.1016/0092-8674(92)90164-8
/ Cell / The small GTP-binding protein rac regulates growth factor-induced membrane ruffling by Ridley (1992)10.1083/jcb.131.3.761
/ J Cell Biol / pp60c-srcis a positive regulator of growth factor-induced cell scattering in a rat bladder carcinoma cell line by Rodier (1995)10.1016/S0092-8674(00)80226-3
/ Cell / Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras by Rodriguez-Viciana (1997)10.1002/j.1460-2075.1994.tb06684.x
/ EMBO (Eur Mol Biol Organ) J / A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner by Sakai (1994)10.1128/MCB.17.3.1702
/ Mol Cell Biol / Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130 CAS and Nck adaptor proteins by Schlaepfer (1997)10.1074/jbc.270.25.15341
/ J Biol Chem / The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps 15 and Eps 15R by Schumacher (1995)10.1146/annurev.cb.11.110195.003001
/ Annu Rev Cell Dev Biol / Integrins: emerging paradigms of signal transduction by Schwartz (1995){'key': '2023072823032213400_B39', 'first-page': '72', 'article-title': 'Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility', 'volume': '13', 'author': 'Takaishi', 'year': '1993', 'journal-title': 'Mol Cell Biol'}
/ Mol Cell Biol / Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility by Takaishi (1993){'key': '2023072823032213400_B40', 'first-page': '4409', 'article-title': 'Both the SH2 and SH3 domains of human Crk protein are required for neuronal differentiation of PC12 cells', 'volume': '13', 'author': 'Tanaka', 'year': '1993', 'journal-title': 'Mol Cell Biol'}
/ Mol Cell Biol / Both the SH2 and SH3 domains of human Crk protein are required for neuronal differentiation of PC12 cells by Tanaka (1993)10.1074/jbc.270.38.22259
/ J Biol Chem / Tyrosine phosphorylation of p130Cas and cortactin accompanies integrin-mediated cell adhesion to the extracellular matrix by Vuori (1995)10.1128/MCB.16.6.2606
/ Mol Cell Biol / Induction of p130Cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases by Vuori (1996)10.1247/csf.13.281
/ Cell Struct Funct / Novel purification of vitronectin from human plasma by heparin affinity chromatography by Yatohgo (1988)
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:47 p.m.) |
Deposited | 2 years ago (July 28, 2023, 7:04 p.m.) |
Indexed | 8 hours, 26 minutes ago (Aug. 27, 2025, 12:06 p.m.) |
Issued | 27 years, 6 months ago (Feb. 23, 1998) |
Published | 27 years, 6 months ago (Feb. 23, 1998) |
Published Online | 27 years, 6 months ago (Feb. 23, 1998) |
Published Print | 27 years, 6 months ago (Feb. 23, 1998) |
@article{Klemke_1998, title={CAS/Crk Coupling Serves as a “Molecular Switch” for Induction of Cell Migration}, volume={140}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.140.4.961}, DOI={10.1083/jcb.140.4.961}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Klemke, Richard L. and Leng, Jie and Molander, Rachel and Brooks, Peter C. and Vuori, Kristiina and Cheresh, David A.}, year={1998}, month=feb, pages={961–972} }