Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells

Serge N. Manié, Andreas R.P. Beck, Anne Astier, Susan F. Law, Tim Canty, Hisamaru Hirai, Brian J. Druker, Hava Avraham, Nilou Haghayeghi, Martin Sattler, Ravi Salgia, James D. Griffin, Erica A. Golemis, Arnold S. Freedman

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105 Scopus citations

Abstract

The Crk-associated substrate p130(Cas) (Cas) and the recently described human enhancer of filamentation 1 (HEF1) are two proteins with similar structure (64% amino acid homology), which are thought to act as 'docking' molecules in intracellular signaling cascades. Both proteins contain an N- terminal Src homology (SH), three domain and a cluster of SB2 binding motifs. Here we show that ligation of either β1 integrin or B cell antigert receptor (BCR) on human tonsillar B cells and B cell lines promoted tyrosine phosphorylation of HEF1. In contrast, Cas tyrosine phosphorylation was observed in certain B cell lines but not in tonsillar B cells, indicating a more general role for HEEl in B cell signaling. Interestingly, pretreatment of tonsillar B cells with cytochalasin B dramatically reduced both integrin- and BCR-induced HEF1 phosphorylation, suggesting that some component of the BCR-mediated signaling pathway is closely linked with a cytoskeletal reorganization. Both HEF1 and Cas were found to complex with the related adhesion focal tyrosine kinase (RAFTK), and when tyrosine phosphorylated, with the adapter molecule CrkL. In addition, the two molecules were detected in p53/56(Lyn) immunoprecipitates, and Lyn kinase was found to specifically bind the C-terminal proline-rich sequence of Cas in an in vitro binding assay. These associations implicate HEF1 and Cas as important components in a cytoskeleton-linked signaling pathway initiated by ligation of β1 integrin or BCR on human B cells.

Original languageEnglish (US)
Pages (from-to)4230-4236
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number7
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Manié, S. N., Beck, A. R. P., Astier, A., Law, S. F., Canty, T., Hirai, H., Druker, B. J., Avraham, H., Haghayeghi, N., Sattler, M., Salgia, R., Griffin, J. D., Golemis, E. A., & Freedman, A. S. (1997). Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. Journal of Biological Chemistry, 272(7), 4230-4236. https://doi.org/10.1074/jbc.272.7.4230