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Differential Signaling after β1 Integrin Ligation Is Mediated Through Binding of CRKL to p120CBL and p110HEF1
Sattler, Martin Salgia, Ravi Shrikhande, Gautam Verma, Shalini Uemura, Naoki Law, Susan F. Griffin, James D.
Sattler, Martin
Salgia, Ravi
Shrikhande, Gautam
Verma, Shalini
Uemura, Naoki
Law, Susan F.
Griffin, James D.
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Journal article
Date
1997-05-30
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Cancer and Cellular Biology
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http://dx.doi.org/10.1074/jbc.272.22.14320
Abstract
CRKL is an SH2-SH3-SH3 adapter protein that is a major substrate of the BCR/ABL oncogene. The function of CRKL in normal cells is unknown. In cells transformed by BCR/ABL we have previously shown that CRKL is associated with two focal adhesion proteins, tensin and paxillin, suggesting that CRKL could be involved in integrin signaling. In two hematopoietic cell lines, MO7e and H9, we found that CRKL rapidly associates with tyrosine-phosphorylated proteins after cross-linking of β1 integrins with fibronectin or anti-β1 integrin monoclonal antibodies. The major tyrosine-phosphorylated CRKL-binding protein in the megakaryocytic MO7e cells was identified as p120CBL, the cellular homolog of the v-Cbl oncoprotein. However, in the lymphoid H9 cell line, the major tyrosine-phosphorylated CRKL-binding protein was p110HEF1. In both cases, this binding was mediated by the CRKL SH2 domain. Interestingly, although both MO7e and H9 cells express p120CBLand p110HEF1, β1 integrin cross-linking induces tyrosine phosphorylation of p120CBL (but not p110HEF1) in MO7e cells and of p110HEF1 (but not p120CBL) in H9 cells. In both cell types, CRKL is constitutively complexed to C3G, SOS, and c-ABL through its SH3 domains, and the stoichiometry of these complexes does not change upon integrin ligation. Thus, in different cell types CRKL and its SH3-associated proteins may form different multimeric complexes depending on whether p120CBL or p110HEF1 is tyrosine-phosphorylated after integrin ligation. The shift in association of CRKL and its SH3-associated proteins from p120CBL to p110HEF1 could contribute to different functional outcomes of “outside-in” integrin signaling in different cells.
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Citation
Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD. Differential Signaling after β1 Integrin Ligation Is Mediated Through Binding of CRKL to p120CBL and p110HEF1. J Biol Chem. 1997 May 30;272(22):14320-14326. doi:10.1074/jbc.272.22.14320.
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Elsevier
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Journal of Biological Chemistry, Vol. 272, Iss. 22
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