Abstract
A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56lck has been identified. The additional presence of the unique N-terminal region of p56lck prevents p62 binding to the SH2 domain. However, phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62. Moreover, p62 is associated with a serine/threonine kinase activity and also binds to ras GTPase-activating protein, a negative regulator of the ras signaling pathway. Thus, phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Cell Line
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GTPase-Activating Proteins
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Glutathione Transferase / metabolism
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HeLa Cells
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Homeostasis
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Humans
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Molecular Sequence Data
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Molecular Weight
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Mutagenesis, Site-Directed
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Peptide Fragments / chemistry
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Peptide Fragments / isolation & purification
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Peptide Fragments / metabolism
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Phosphoserine / metabolism
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Phosphotyrosine
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Protein Serine-Threonine Kinases / metabolism
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Proteins / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Serine
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Transfection
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ras GTPase-Activating Proteins
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src Homology Domains*
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src-Family Kinases / chemistry
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src-Family Kinases / metabolism*
Substances
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GTPase-Activating Proteins
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Peptide Fragments
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Proteins
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Recombinant Fusion Proteins
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ras GTPase-Activating Proteins
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Phosphoserine
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Phosphotyrosine
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Serine
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Glutathione Transferase
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases
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Protein Serine-Threonine Kinases