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Originally published In Press as doi:10.1074/jbc.M002831200 on July 10, 2000
J. Biol. Chem., Vol. 275, Issue 38, 29754-29760, September 22, 2000
Cell Swelling-induced Translocation of Rat Liver
Na+/Taurocholate Cotransport Polypeptide Is Mediated via
the Phosphoinositide 3-Kinase Signaling Pathway*
Cynthia R. L.
Webster,
Christopher J.
Blanch,
Jeffrey
Phillips, and
M. Sawkat
Anwer
From the Department of Biomedical Sciences, Tufts University School
of Veterinary Medicine, North Grafton, Massachusetts 01536
Cell swelling stimulates phosphoinositide
3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) in
hepatocytes, and the PI3K signaling pathway is involved in
cAMP-mediated translocation of sinusoidal
Na+/taurocholate (TC) cotransporter (Ntcp) to the
plasma membrane. We determined whether cell swelling also stimulates TC
uptake and Ntcp translocation via the PI3K and/or MAPK signaling
pathway. All studies were conducted in isolated rat hepatocytes.
Hepatocyte swelling induced by hypotonic media resulted in: 1)
time- and medium osmolarity-dependent increases in TC
uptake, 2) an increase in the Vmax of
Na+/TC cotransport, and 3) wortmannin-sensitive increases
in TC uptake and plasma membrane Ntcp mass. Hepatocyte swelling also
induced wortmannin-sensitive activation of PI3K, protein kinase
B, and p70S6K. Rapamycin, an inhibitor of
p70S6K, inhibited cell swelling-induced activation of
p70S6K but failed to inhibit cell swelling-induced
stimulation of TC uptake. Because PD98095, an inhibitor of MAPK, did
not inhibit cell swelling-induced increases in TC uptake, it is
unlikely that the effect of cell swelling on TC uptake is mediated via
the MAPK signaling pathway. Taken together, these results indicate that 1) cell swelling stimulates TC uptake by translocating Ntcp to the
plasma membrane, 2) this effect is mediated via the PI3K, but not MAPK,
signaling pathway, and 3) protein kinase B, but not p70S6K,
is a likely downstream effector of PI3K.
*
This work was supported in part by Grant DK-33436 from the
National Institutes of Health.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biomedical
Sciences, Tufts University School of Veterinary Medicine, 200 Westboro
Rd., North Grafton, MA 01536. Tel.: 508-839-8788; Fax: 508-839-8787;
E-mail: SANWER@INFONET.TUFTS.EDU.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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