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Involvement of p130Cas and p105HEF1, a Novel Cas-like Docking Protein, in a Cytoskeleton-dependent Signaling Pathway Initiated by Ligation of Integrin or Antigen Receptor on Human B Cells

Manié, Serge N.
Beck, Andreas R.P.
Astier, Anne
Law, Susan F.
Canty, Tim
Hirai, Hisamaru
Druker, Brian J.
Avraham, Hava
Haghayeghi, Nilou
Sattler, Martin
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Journal article
Date
1997-02-14
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Cancer and Cellular Biology
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DOI
http://dx.doi.org/10.1074/jbc.272.7.4230
Abstract
The Crk-associated substrate p130Cas (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 SH2 binding motifs. Here we show that ligation of either β1 integrin or B cell antigen 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 HEF1 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 p53/56Lyn 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.
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Citation
Manié SN, Beck ARP, Astier A, Law SF, Canty T, Hirai H, et al. Involvement of p130Cas and p105HEF1, a Novel Cas-like Docking Protein, in a Cytoskeleton-dependent Signaling Pathway Initiated by Ligation of Integrin or Antigen Receptor on Human B Cells. J Biol Chem. 1997 Feb 14;272(7):4230-4236. doi:10.1074/jbc.272.7.4230.
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Elsevier
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Journal of Biological Chemistry, Vol. 272, Iss. 7
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