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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2010-2-25
pubmed:abstractText
The serum- and glucocorticoid-inducible kinase SGK1 and the protein kinase PKB/Akt presumably phosphorylate and, by this means, activate the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3), which has in turn been shown to regulate transporters and channels. SGK1-regulated channels include the Ca(2+) channel TRPV6, which is expressed in a variety of epithelial and nonepithelial cells including tumor cells. SGK1 and protein kinase B PKB/Akt foster tumor growth. The present study thus explored whether TRPV6 is regulated by PIKfyve. TRPV6 was expressed in Xenopus laevis oocytes with or without additional coexpression of constitutively active (S422D)SGK1, constitutively active (T308D,S473D)PKB, wild-type PIKfyve, and (S318A)PIKfyve lacking the SGK1 phosphorylation site. TRPV6 activity was determined from the current (I(Ca)) resulting from TRPV6-induced Ca(2+) entry and subsequent activation of Ca(2+)-sensitive endogenous Cl(-) channels. TRPV6 protein abundance in the cell membrane was determined utilizing immunohistochemistry and Western blotting. In TRPV6-expressing oocytes I(H) was increased by coexpression of (S422D)SGK1 and by (T308D,S473D)PKB. Coexpression of wild-type PIKfyve further increased I(H) in TRPV6 + (S422D)SGK1-expressing oocytes but did not significantly modify I(Ca) in oocytes expressing TRPV6 alone. (S318A)PIKfyve failed to significantly modify I(Ca) in the presence and absence of (S422D)SGK1. (S422D)SGK1 increased the TRPV6 protein abundance in the cell membrane, an effect augmented by additional expression of wild-type PIKfyve. We conclude that PIKfyve participates in the regulation of TRPV6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1432-1424
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
233
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-41
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Regulation of the Ca(2+) channel TRPV6 by the kinases SGK1, PKB/Akt, and PIKfyve.
pubmed:affiliation
Department of Physiology I, University of Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't