p62dok: A Constitutively Tyrosine-Phosphorylated, GAP-Associated Protein in Chronic Myelogenous Leukemia Progenitor Cells

Abstract Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p210 bcr-abl protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine-phosphorylated protein that migrates at 62 kDa by SDS–PAGE and associates with the p120 ras GTPase-activating protein (GAP). We have purified p62 dok from a hematopoietic cell line expressing p210 bcr-abl . p62 dok is a novel protein with features of a signaling molecule. Association of p62 dok with GAP correlates with its tyrosine phosphorylation. p62 dok is rapidly tyrosine-phosphorylated upon activation of the c-Kit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases.