Figure 6.

Proposed model for interaction between oncoproteins and G protein-coupled signal transduction pathways in transformed mammalian cells. BCR/ABL oncoprotein interferes with the Src-related kinase Lyn signaling, which is regulated by G protein–coupled chemokine receptors in hematopoietic cells. A previously defined direct interaction of G protein subunits with Src family kinases (references 24 and 27) and linkage of G protein–coupled receptor via Src kinases to the receptor tyrosine kinase complex and its downstream signaling cascades (references 22–28 and 44) is indicated, as described in the text. The signaling paradigm we have depicted provides a mechanism to explain the ability of BCR/ABL, and potentially other oncoproteins, to couple simultaneously to multiple signaling transducers (e.g., PI3-kinase, Shc adaptor protein, receptor tyrosine kinase, and the RAS-to-MAPK cascade). This paradigm may also provide further insight into the remarkable ability of Src family kinases to transform various cell types.