Sloan-kettering Institute for Cancer Research

Cold Spring Harbor Laboratory

David G Wisniewski

Ryuji Kobayashi

Nicholas A Carpino

Bayard D Clarkson

Annabel O'c Strife

Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p120.sup.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 approximately 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). This novel protein, called p62.sup.dok (p62 protein downstream of tyrosine kinases), was isolated from a hematopoietic cell line expressing p120.sup.bcr-abl. Association of p62.sup.dok with GAP correlates with its tyrosine phosphorylation. p62.sup.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.

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Staten Island, NY, United States of America

David G Wisniewski