Direct Binding of C-terminal Region of p130 to SH2 and SH3 Domains of Src Kinase

摘要: Abstract p130 is a major tyrosine-phosphorylated protein that tightly binds v-Crk in v-crk-transformed cells and v-Src v-src-transformed cells. The “substrate domain” of contains 15 possible Src homology (SH) 2-binding motifs, most which conform to the binding motif for Crk SH2 domain. Another region near its C terminus motifs domain proline-rich sequences are candidates SH3-binding sites. Using GST fusion proteins, we revealed both SH3 domains bind p130, whereas through We located site at sequence RPLPSPP terminus. Mutations within this or Tyr caused significant reduction association with Src, no was detected when them were deleted. kinase activity v-Crk-transformed also associated region. On other hand, deletion substrate abolished v-Crk. C-terminal may facilitate effective hyperphosphorylation tyrosine residues resulting SH2-containing molecules p130.