Dok-1 associates with the Ras GTPase-activating protein (Ras GAP) upon tyrosine
phosphorylation. Evidence suggests that Dok-1 (also designated p62dok)
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, are members 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 p56dok)
has also been identified as a potential mediator of the effects of p210 Bcr-Abl.