GSK3β inactivation in podocytes results in decreased phosphorylation of p70S6K accompanied by cytoskeletal rearrangements and inhibited motility
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GSK3β inactivation in podocytes results in decreased phosphorylation of p70S6K accompanied by cytoskeletal rearrangements and inhibited motility. / George, Britta; Vollenbröker, Beate; Saleem, Moin A; Huber, Tobias B; Pavenstädt, Hermann; Weide, Thomas.
in: AM J PHYSIOL-RENAL, Jahrgang 300, Nr. 5, 05.2011, S. F1152-62.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - GSK3β inactivation in podocytes results in decreased phosphorylation of p70S6K accompanied by cytoskeletal rearrangements and inhibited motility
AU - George, Britta
AU - Vollenbröker, Beate
AU - Saleem, Moin A
AU - Huber, Tobias B
AU - Pavenstädt, Hermann
AU - Weide, Thomas
PY - 2011/5
Y1 - 2011/5
N2 - The inhibition of mTOR kinase after renal transplantation has been associated with podocyte injury and proteinuria; however, the signaling pathways regulating these effects are not well understood. We found that prolonged rapamycin treatment in podocytes leads to an increase in glycogen synthase kinase 3β (GSK3β) phosphorylation, resulting in inactivation of total GSK3β kinase activity. To investigate the cellular consequences of the inactivation of GSK3β, we used two inhibitors reducing kinase activity and studied the cross talk between GSK3 function and the Akt/mammalian target of rapamycin (mTOR) pathway. Both GSK3 inhibitors reduced the phosphorylation of the mTOR downstream target, p70(S6K), indicating that GSK3 inhibition in podocytes is able to cause similar effects as treatment with rapamycin. Moreover, GSK3 inhibition was accompanied by the reduced expression of slit diaphragm-associated proteins and resulted in an altered cytoskeletal structure and reduced motility of podocytes, suggesting that GSK3 kinase can modulate Akt/mTOR-dependent signaling in podocytes.
AB - The inhibition of mTOR kinase after renal transplantation has been associated with podocyte injury and proteinuria; however, the signaling pathways regulating these effects are not well understood. We found that prolonged rapamycin treatment in podocytes leads to an increase in glycogen synthase kinase 3β (GSK3β) phosphorylation, resulting in inactivation of total GSK3β kinase activity. To investigate the cellular consequences of the inactivation of GSK3β, we used two inhibitors reducing kinase activity and studied the cross talk between GSK3 function and the Akt/mammalian target of rapamycin (mTOR) pathway. Both GSK3 inhibitors reduced the phosphorylation of the mTOR downstream target, p70(S6K), indicating that GSK3 inhibition in podocytes is able to cause similar effects as treatment with rapamycin. Moreover, GSK3 inhibition was accompanied by the reduced expression of slit diaphragm-associated proteins and resulted in an altered cytoskeletal structure and reduced motility of podocytes, suggesting that GSK3 kinase can modulate Akt/mTOR-dependent signaling in podocytes.
KW - Adaptor Proteins, Signal Transducing
KW - Cell Line
KW - Cell Movement
KW - Cytoskeletal Proteins
KW - Cytoskeleton
KW - Humans
KW - Immunosuppressive Agents
KW - Indoles
KW - Lithium Chloride
KW - Maleimides
KW - Membrane Proteins
KW - Nuclear Proteins
KW - Oncogene Proteins
KW - Phosphorylation
KW - Podocytes
KW - Protein Kinase Inhibitors
KW - Proto-Oncogene Proteins c-akt
KW - Ribosomal Protein S6 Kinases, 70-kDa
KW - Signal Transduction
KW - Sirolimus
KW - TOR Serine-Threonine Kinases
KW - Time Factors
KW - WT1 Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1152/ajprenal.00373.2010
DO - 10.1152/ajprenal.00373.2010
M3 - SCORING: Journal article
C2 - 21228102
VL - 300
SP - F1152-62
JO - AM J PHYSIOL-RENAL
JF - AM J PHYSIOL-RENAL
SN - 1931-857X
IS - 5
ER -
