| First Author | Lee BH | Year | 2004 |
| Journal | Mol Cell | Volume | 15 |
| Issue | 5 | Pages | 741-51 |
| PubMed ID | 15350218 | Mgi Jnum | J:92516 |
| Mgi Id | MGI:3053253 | Doi | 10.1016/j.molcel.2004.07.018 |
| Citation | Lee BH, et al. (2004) WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding. Mol Cell 15(5):741-51 |
| abstractText | WNK (with no lysine [K]) protein kinases were named for their unique active site organization. Mutations in WNK1 and WNK4 cause a familial form of hypertension by undefined mechanisms. Here, we report that WNK1 selectively binds to and phosphorylates synaptotagmin 2 (Syt2) within its calcium binding C2 domains. Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. These findings provide a biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. Interruption of this regulatory pathway may disturb membrane events that regulate ion balance. |
