Tyrosine phosphorylation of the product of the c-cbl protooncogene is [corrected] induced after integrin stimulation

S N Manié, 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 journalArticlepeer-review

Abstract / Description of output

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 p125FAK. Here we show that the c-CBL protooncogene product p120c-CBL is a component of these substrates. beta 1 integrin stimulation of p120c-CBL phosphorylation was observed in both transformed and normal human B cells, and was inhibited by prior treatment of cells with cytochalasin B, which disrupts the actin network. In contrast, tyrosine phosphorylation of p120c-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 p120c-CBL. In MO7e cells, this stimulation was induced by ligation of either beta 1 or beta 2 integrin, whereas only by ligation of beta 1 integrin in B cells. Tyrosine phosphorylation of p120c-CBL links phosphatidylinositol-3 kinase (PI-3K) with the BCR signaling machinery. Although the p85 subunit of PI-3K was increased in p120c-CBL immunoprecipitates from BCR-stimulated B cells, this association was only minimally increased by beta 1 integrin ligation. The function of p120c-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 p120c-CBL has a significant function in signal transduction pathways, and therefore may play a role in integrin signaling in lymphoid and hematopoietic cells.
Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalExperimental Hematology
Issue number1
Publication statusPublished - 1997

Keywords / Materials (for Non-textual outputs)

  • B-Lymphocytes
  • Cell Line
  • Humans
  • Integrins
  • Phosphorylation
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-cbl
  • Signal Transduction
  • Tyrosine
  • Ubiquitin-Protein Ligases


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