WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding

Byung Hoon Lee, Xiaoshan Min, Charles J. Heise, Bing E. Xu, She Chen, Hongjun Shu, Kate Luby-Phelps, Elizabeth J. Goldsmith, Melanie H. Cobb

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


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 Ca 2+-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.

Original languageEnglish (US)
Pages (from-to)741-751
Number of pages11
JournalMolecular cell
Issue number5
StatePublished - Sep 10 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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