Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region

Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12338-42. doi: 10.1073/pnas.92.26.12338.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • GTPase-Activating Proteins
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Homeostasis
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Molecular Sequence Data
  • Molecular Weight
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism
  • Phosphoserine / metabolism
  • Phosphotyrosine
  • Protein Serine-Threonine Kinases / metabolism
  • Proteins / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Serine
  • Transfection
  • ras GTPase-Activating Proteins
  • src Homology Domains*
  • src-Family Kinases / chemistry
  • src-Family Kinases / metabolism*

Substances

  • GTPase-Activating Proteins
  • Peptide Fragments
  • Proteins
  • Recombinant Fusion Proteins
  • ras GTPase-Activating Proteins
  • Phosphoserine
  • Phosphotyrosine
  • Serine
  • Glutathione Transferase
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases
  • Protein Serine-Threonine Kinases