Tyrosine phosphorylated proteins in chronic myelogenous leukemia.
An aberrantly expressed and highly active abl tyrosine kinase (p210bcr-abl) appears critical for the development and pathogenesis of chronic myelogenous-leukemia (CML). CML cells and cell lines each displayed a similar spectrum of phosphotyrosyl proteins. Analysis of these proteins by glycerol-gradient ultracentrifugation showed that many apparently existed as multimeric complexes. Confirming this, several of these proteins co-immunoprecipitated, along with the p210bcr-abl, with antibody to abl. Included were co-precipitating proteins identified as the p120 ras GTPase-activating protein (GAP) and the p62 protein that binds both to GAP and to a number of other tyrosine-phosphorylated proteins having peptide regions homologous to the second domain of src. Because p62, ras GAP and ras are involved in growth-factor and oncogene activation of cells, this pathway may also play an important role in CML.
Frackelton
A R
AR
Department of Medicine, Brown University and Roger Williams Medical Center, Province, Rhode Island 02908.
Kumar
P S
PS
Kannan
B
B
Clark
J W
JW
D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000302:isolation & purification*; D010750:Phosphoproteins / Q000302:isolation & purification*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014461:Ultracentrifugation; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl