Regulation of the Ca2+ Channel TRPV6 by the Kinases SGK1, PKB/Akt, and PIKfyve

Regulation of the Ca2+ Channel TRPV6 by the Kinases SGK1, PKB/Akt, and PIKfyve 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 Ca2+ 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 S422DSGK1, constitutively active T308D,S473DPKB, wild-type PIKfyve, and S318APIKfyve lacking the SGK1 phosphorylation site. TRPV6 activity was determined from the current (ICa) resulting from TRPV6-induced Ca2+ entry and subsequent activation of Ca2+-sensitive endogenous Cl− channels. TRPV6 protein abundance in the cell membrane was determined utilizing immunohistochemistry and Western blotting. In TRPV6-expressing oocytes IH was increased by coexpression of S422DSGK1 and by T308D,S473DPKB. Coexpression of wild-type PIKfyve further increased IH in TRPV6 + S422DSGK1-expressing oocytes but did not significantly modify ICa in oocytes expressing TRPV6 alone. S318APIKfyve failed to significantly modify ICa in the presence and absence of S422DSGK1. S422DSGK1 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Regulation of the Ca2+ Channel TRPV6 by the Kinases SGK1, PKB/Akt, and PIKfyve

Loading next page...
 
/lp/springer_journal/regulation-of-the-ca2-channel-trpv6-by-the-kinases-sgk1-pkb-akt-and-rABoB4zBK5
Publisher
Springer-Verlag
Copyright
Copyright © 2009 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-009-9222-0
Publisher site
See Article on Publisher Site

Abstract

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 Ca2+ 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 S422DSGK1, constitutively active T308D,S473DPKB, wild-type PIKfyve, and S318APIKfyve lacking the SGK1 phosphorylation site. TRPV6 activity was determined from the current (ICa) resulting from TRPV6-induced Ca2+ entry and subsequent activation of Ca2+-sensitive endogenous Cl− channels. TRPV6 protein abundance in the cell membrane was determined utilizing immunohistochemistry and Western blotting. In TRPV6-expressing oocytes IH was increased by coexpression of S422DSGK1 and by T308D,S473DPKB. Coexpression of wild-type PIKfyve further increased IH in TRPV6 + S422DSGK1-expressing oocytes but did not significantly modify ICa in oocytes expressing TRPV6 alone. S318APIKfyve failed to significantly modify ICa in the presence and absence of S422DSGK1. S422DSGK1 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.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Dec 30, 2009

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off