The related adhesion focal tyrosine kinase differentially phosphorylates p130(Cas) and the Cas-like protein, p105(HEF1)

Anne Astier, Serge N. Manié, Hava Avraham, Hisamaru Hirai, Susan F. Law, Yuzhu Zhang, Erica A. Golemis, Yigong Fu, Brian J. Druker, Nilou Haghayeghi, Arnold S. Freedman, Shalom Avraham

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93 Scopus citations

Abstract

The related adhesion focal tyrosine kinase (RAFTK) is tyrosine- phosphorylated following β1 integrin or B cell antigen receptor stimulation in human B cells. Two substrates that are tyrosine-phosphorylated following integrin ligation in B cells are p130(Cas) and the Cas family member human enhancer of filamentation 1 (HEF1), both of which can associate with RAFTK. In this report we observed that RAFTK was involved in the phosphorylation of these two proteins. While a catalytically active RAFTK was required for both p130(Cas) and HEF1, phosphorylation of p130(Cas), but not of HEF1, was dependent on an intact autophosphorylation site (Tyr402) on RAFTK. To determine if RAFTK phosphorylated p130(Cas) and HEF1 directly or through an intermediate, we assayed the ability of RAFTK and of a Tyr402 mutant to phosphorylate purified HEF1 and p130(Cas) domains. RAFTK was able to phosphorylate the substrate domains of both p130(Cas) and HEF1, but only the C-terminal domain of p130(Cas). Furthermore, Tyr402, which mediates the binding of RAFTK to c-Src kinase, was required for the phosphorylation of the C-terminal domain of p130(Cas). These data suggest that RAFTK itself is sufficient for HEF1 phosphorylation, whereas a cooperation between RAFTK and Src kinases is required for the complete phosphorylation of p130(Cas).

Original languageEnglish (US)
Pages (from-to)19719-19724
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number32
DOIs
StatePublished - Aug 8 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Astier, A., Manié, S. N., Avraham, H., Hirai, H., Law, S. F., Zhang, Y., Golemis, E. A., Fu, Y., Druker, B. J., Haghayeghi, N., Freedman, A. S., & Avraham, S. (1997). The related adhesion focal tyrosine kinase differentially phosphorylates p130(Cas) and the Cas-like protein, p105(HEF1). Journal of Biological Chemistry, 272(32), 19719-19724. https://doi.org/10.1074/jbc.272.32.19719