P62(DOK) - A CONSTITUTIVELY TYROSINE-PHOSPHORYLATED, GAP-ASSOCIATED PROTEIN IN CHRONIC MYELOGENOUS LEUKEMIA PROGENITOR CELLS

Characteristic of chronic myelogenous leukemia (CML) is the presence o f the chimeric p210(bcr-abl) protein possessing elevated protein tyros ine kinase activity relative to normal c-abl tyrosine kinase. Hematopo ietic progenitors isolated from CML patients in the chronic phase cont ain 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 lin e expressing p210(bcr-abl). p62(dok) is a novel protein with features of a signaling molecule. Association of p62(dok) with GAP correlates w ith its tyrosine phosphorylation. p62(dok) is rapidly tyrosine-phospho rylated upon activation of the c-Kit receptor, implicating it as a com ponent of a signal transduction pathway downstream of receptor tyrosin e kinases.