Tyrosine phosphorylation of the product of the c-cbl protooncogenesis induced after integrin stimulation

S. N. Manie, M. Sattler, A. Astier, J. S. Phifer, T. Canty, C. Morimoto, B. J. Druker, R. Salgia, J. D. Griffin, A. S. Freedman

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Integrin crosslinking on human B cells induces tyrosine phosphorylation of a set of proteins ranging from 105 to 130 kDa, among which is the focal adhesion kinase p125(FAK). Here we show that the c-CBL protooncogene product p120(c-CBL) is a component of these substrates. β1 integrin stimulation of p120(c-CBL) phosphorylation was observed in both transformed and normal human B cells, and was inbibited by prior treatment of cells with cytochalasin B, which disrupts the actin network. In contrast, tyrosine phosphorylation of p120(c-CBL) following crosslinking of the B cell antigen receptor (BCR) was not affected by cytochalasin B. Integrin stimulation of the promegakaryocytic cell line MO7e also led to a cytoskeleton-dependent tyrosine phosphorylation of p120(c-CBL). In MO7e cells, this stimulation was induced by ligation of either β1 or β2 integrin, whereas only by ligation of β1 integrin in B cells. Tyrosine phosphorylation of p120(c-CBL) links phosphatidylinositol-3 kinase (pI-3K) with the BCR signalling machinery. Although the p85 subunit of PI-3K was increased in p120(c-CBL) immunoprecipitates from BCR-stimulated B cells, this association was only minimally increased by β1 integrin ligation. the function of p120(c-CBL) remains unknown; however, its interactions in vitro and in vivo with Src homology 2 and 3 (SH2 and SH3) domain-containing proteins suggest that p120(c-CBL) has a significant function in signal transduction pathways, and therefore may play a role in integrin signalling in lymphoid and hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalExperimental hematology
Volume25
Issue number1
StatePublished - 1997

Keywords

  • B cells
  • cbl
  • integrin
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Manie, S. N., Sattler, M., Astier, A., Phifer, J. S., Canty, T., Morimoto, C., Druker, B. J., Salgia, R., Griffin, J. D., & Freedman, A. S. (1997). Tyrosine phosphorylation of the product of the c-cbl protooncogenesis induced after integrin stimulation. Experimental hematology, 25(1), 45-50.