The PDGF receptor phosphorylates Tyr 138 in the c-Src SH3 domain in vivo reducing peptide ligand binding

Oncogene. 1997 Jan 9;14(1):17-34. doi: 10.1038/sj.onc.1200798.


Treatment of quiescent NIH3T3 cells with PDGF BB results in the transient activation and hyperphosphorylation of the protein-tyrosine kinase, c-Src. These effects correlate with novel serine and tyrosine phosphorylations in the N-terminal non-catalytic region of the molecule, which contains an SH3 and SH2 domain. In this study, a site of PDGF-induced tyrosine phosphorylation was mapped to Tyr 138 in the SH3 domain; Tyr 138 is exposed on the SH3 peptide binding surface. This same site is phosphorylated in vitro by the PDGF receptor when purified baculovirus-expressed c-Src is complexed with the activated receptor. Phosphorylation of Tyr 138 required association of c-Src with the PDGF receptor via its SH2 domain. When a c-Src Phe 138 mutant was stably expressed in Src- mouse fibroblasts, it was activated to the same extent as wild type c-Src following PDGF stimulation, indicating that phosphorylation of this site is not required for PDGF-mediated activation. However, Tyr 138 phosphorylation was found to diminish SH3 domain peptide ligand binding ability in vitro.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cells, Cultured
  • Mice
  • Molecular Sequence Data
  • Peptide Mapping
  • Phosphorylation
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / isolation & purification
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Platelet-Derived Growth Factor / metabolism*
  • Recombinant Proteins / isolation & purification
  • Sequence Alignment
  • Spodoptera
  • Tyrosine / metabolism*
  • src Homology Domains* / physiology
  • src-Family Kinases


  • Platelet-Derived Growth Factor
  • Recombinant Proteins
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases