| First Author | Huang Z | Year | 2016 |
| Journal | Mol Cell | Volume | 61 |
| Issue | 1 | Pages | 98-110 |
| PubMed ID | 26687682 | Mgi Jnum | J:232812 |
| Mgi Id | MGI:5780255 | Doi | 10.1016/j.molcel.2015.11.010 |
| Citation | Huang Z, et al. (2016) Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cgamma. Mol Cell 61(1):98-110 |
| abstractText | The molecular basis by which receptor tyrosine kinases (RTKs) recruit and phosphorylate Src Homology 2 (SH2) domain-containing substrates has remained elusive. We used X-ray crystallography, NMR spectroscopy, and cell-based assays to demonstrate that recruitment and phosphorylation of Phospholipase Cgamma (PLCgamma), a prototypical SH2 containing substrate, by FGF receptors (FGFR) entails formation of an allosteric 2:1 FGFR-PLCgamma complex. We show that the engagement of pTyr-binding pocket of the cSH2 domain of PLCgamma by the phosphorylated tail of an FGFR kinase induces a conformational change at the region past the cSH2 core domain encompassing Tyr-771 and Tyr-783 to facilitate the binding/phosphorylation of these tyrosines by another FGFR kinase in trans. Our data overturn the current paradigm that recruitment and phosphorylation of substrates are carried out by the same RTK monomer in cis and disclose an obligatory role for receptor dimerization in substrate phosphorylation in addition to its canonical role in kinase activation. |
