| First Author | Akbulut S | Year | 2010 |
| Journal | Mol Biol Cell | Volume | 21 |
| Issue | 19 | Pages | 3487-96 |
| PubMed ID | 20719962 | Mgi Jnum | J:182830 |
| Mgi Id | MGI:5316941 | Doi | 10.1091/mbc.E10-02-0123 |
| Citation | Akbulut S, et al. (2010) Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C. Mol Biol Cell 21(19):3487-96 |
| abstractText | Sprouty (Spry) proteins are negative regulators of receptor tyrosine kinase signaling; however, their exact mechanism of action remains incompletely understood. We identified phosphatidylinositol-specific phospholipase C (PLC)-gamma as a partner of the Spry1 and Spry2 proteins. Spry-PLCgamma interaction was dependent on the Src homology 2 domain of PLCgamma and a conserved N-terminal tyrosine residue in Spry1 and Spry2. Overexpression of Spry1 and Spry2 was associated with decreased PLCgamma phosphorylation and decreased PLCgamma activity as measured by production of inositol (1,4,5)-triphosphate (IP(3)) and diacylglycerol, whereas cells deficient for Spry1 or Spry1, -2, and -4 showed increased production of IP(3) at baseline and further increased in response to growth factor signals. Overexpression of Spry 1 or Spry2 or small-interfering RNA-mediated knockdown of PLCgamma1 or PLCgamma2 abrogated the activity of a calcium-dependent reporter gene, suggesting that Spry inhibited calcium-mediated signaling downstream of PLCgamma. Furthermore, Spry overexpression in T-cells, which are highly dependent on PLCgamma activity and calcium signaling, blocked T-cell receptor-mediated calcium release. Accordingly, cultured T-cells from Spry1 gene knockout mice showed increased proliferation in response to T-cell receptor stimulation. These data highlight an important action of Spry, which may allow these proteins to influence signaling through multiple receptors. |
