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Okadaic acid, sphingosine, and phorbol ester reversibly modulate heat induction on protein kinase F a /GSK‐3α in A431 cells
Author(s) -
Yang ShiawDer,
Chang HsiouChen,
Lee ShanChih
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19960201)60:2<218::aid-jcb6>3.0.co;2-#
Subject(s) - okadaic acid , protein kinase c , protein kinase a , sphingosine , kinase , phosphatase , mitogen activated protein kinase kinase , microbiology and biotechnology , signal transduction , dephosphorylation , phorbol , protein kinase r , biochemistry , chemistry , biology , phosphorylation , receptor
Exposure of A431 cells to a rapid and sudden increase from 37°C to 46°C for 30 min could induce an increase in protein level and cellular activity of protein (kinase F a /GSK‐3α) up to ∼200% of control level. However, when cells were first treated with 500 nM tumor promoter phorbol ester TPA at 37°C for 30 min to activate cellular protein kinase C (PKC) or with 400 nM okadaic acid at 37°C for 30 min to inhibit cellular protein phosphatases followed by heat shock at 46°C for another 30 min, the heat induction on kinase F a /GSK‐3α was found to be completed blocked. In sharp contrast, when cells were first treated with 1 μM TPA at 37°C for 24 h or with 5 μM sphingosine at 37°C for 30 min to down‐regulate cellular PKC, the heat induction on kinase F a /GSK‐3α was found to be reversely promoted up to ∼ 250% of control level, demonstrating that kinase F a /GSK‐3α may not represent a constitutively active/mitogen‐inactivated protein kinase as previously conceived. Taken together, the results provide initial evidence that TPA/sphingosine and okadaic acid could reversibly modulate the heat induction on kinase F a /GSK‐3α in A431 cells, suggesting that phosphorylation/dephosphorylation mechanisms are involved in the regulation of the heat‐shock induction of kinase F a /GSK‐3α, representing a new mode of signal transduction for the regulation of this multisubstrate protein kinase and a new mode of signaling pathway modulating the heat‐induction process. © 1996 Wiley‐Liss, Inc.