PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation.
Binding of platelet-derived growth factor (PDGF) to its receptors leads to the activation of members of the Src family of protein tyrosine kinases. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn.
Hansen
K
K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Alonso
G
G
Courtneidge
S A
SA
Rönnstrand
L
L
Heldin
C H
CH
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D004252:DNA Mutational Analysis; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases