title: The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity.
abstract: Protein tyrosine kinases participate in the transduction and modulation of signals that regulate proliferation and differentiation of cells. Excessive or deregulated protein tyrosine kinase activity can cause malignant transformation. The catalytic activity of the T cell protein tyrosine kinase p56lck is normally suppressed by phosphorylation of a carboxyl-terminal tyrosine, Tyr-505, by another cellular protein tyrosine kinase. Here we characterize a human cytosolic 50 kDa protein tyrosine kinase, p50csk, which specifically phosphorylates Tyr-505 of p56lck and a synthetic peptide containing this site. Phosphorylation of Tyr-505 suppressed the catalytic activity of p56lck. We suggest that p50csk negatively regulates p56lck, and perhaps other cellular src family kinases.
authors.affiliation: Department of Pathology, University of Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Bergman
authors.forename: T
authors.initials: T
authors.lastname: Mustelin
authors.forename: C
authors.initials: C
authors.lastname: Oetken
authors.forename: J
authors.initials: J
authors.lastname: Partanen
authors.forename: N A
authors.initials: NA
authors.lastname: Flint
authors.forename: K E
authors.initials: KE
authors.lastname: Amrein
authors.forename: M
authors.initials: M
authors.lastname: Autero
authors.forename: P
authors.initials: P
authors.lastname: Burn
authors.forename: K
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000595:Amino Acid Sequence; D000081247:CSK Tyrosine-Protein Kinase; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000201:enzymology*; D014162:Transfection; D014357:Trypsin; D014443:Tyrosine; D019061:src-Family Kinases
chemical_list: D010446:Peptide Fragments; D010748:Phosphopeptides; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; C000631346:CSK protein, human; D014357:Trypsin