Dok-1 associates with the Ras GTPase activating protein (Ras GAP) upon
tyrosine phosphorylation. Evidence suggests that p62 Dok-1 is a substrate of
the constitutive tyrosine kinase activity of p210 Bcr-Abl, a fusion protein
caused by the t(9;22) translocation and associated with chronic myelogenous
leukemia. Dok-1, as well as the tyrosine kinase substrates IRS-1 and Cas,
is a member of a class of “docking” proteins which contain multiple tyrosine
residues and putative SH2 binding sites. Dok-1 is suspected to be the substrate
phosphorylated in response to stimulation by a number of growth
factors, including PDGF, VEGF, Insulin and IGF. Dok-2 (also designated p56 Dok)
has also been identified as a potential mediator of the effects of p210 Bcr-Abl.