p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells.
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.
Carpino
N
N
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Wisniewski
D
D
Strife
A
A
Marshak
D
D
Kobayashi
R
R
Stillman
B
B
Clarkson
B
B
D000081247:CSK Tyrosine-Protein Kinase; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020703:ras GTPase-Activating Proteins; D018909:src Homology Domains; D019061:src-Family Kinases
D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C074561:GAP-associated protein p62; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; D016601:RNA-Binding Proteins; D019089:Stem Cell Factor; D020703:ras GTPase-Activating Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D000081247:CSK Tyrosine-Protein Kinase; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases; C000631346:CSK protein, human