Tyrosine phosphorylation of the product of the c-cbl protooncogene is [corrected] induced after integrin stimulation
Manié, S.N.; Sattler, M.; Astier, A.; Phifer, J.S.; Canty, T.; Morimoto, C.; Druker, B.J.; Salgia, R.; Griffin, J.D.; Freedman, A.S.
Experimental Hematology 25(1): 45-50
1997
ISSN/ISBN: 0301-472X PMID: 8989906 Document Number: 478903
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. beta-1 integrin stimulation of p120-c-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 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 beta-1 or beta-2 integrin, whereas only by ligation of beta-1 integrin in B cells. Tyrosine phosphorylation of p120-c-CBL links phosphatidylinositol-3 kinase (PI-3K) with the BCR signaling 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 beta-1 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 signaling in lymphoid and hematopoietic cells.