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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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CSK Tyrosine-Protein Kinase
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Cloning, Molecular
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DNA-Binding Proteins*
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Electrophoresis, Polyacrylamide Gel
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Fusion Proteins, bcr-abl / metabolism
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GTPase-Activating Proteins
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Hematopoietic Stem Cells / metabolism*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
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Phosphoproteins / chemistry
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Phosphoproteins / isolation & purification
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Phosphoproteins / metabolism*
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism*
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Proto-Oncogene Proteins c-kit / metabolism
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RNA-Binding Proteins*
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Signal Transduction
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Stem Cell Factor / metabolism
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Tumor Cells, Cultured
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ras GTPase-Activating Proteins
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src Homology Domains
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src-Family Kinases
Substances
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DNA-Binding Proteins
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DOK1 protein, human
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GAP-associated protein p62
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GTPase-Activating Proteins
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Phosphoproteins
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Proteins
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RNA-Binding Proteins
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Stem Cell Factor
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ras GTPase-Activating Proteins
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Phosphotyrosine
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-kit
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CSK Tyrosine-Protein Kinase
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Fusion Proteins, bcr-abl
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src-Family Kinases
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CSK protein, human