Okadaic acid, sphingosine, and phorbol ester reversibly modulate heat induction on protein kinase Fa/GSK-3α in A431 cells

✍ Scribed by Shiaw-Der Yang; Hsiou-Chen Chang; Shan-Chih Lee

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 789 KB
• Volume: 60
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960201)60:2<218::aid-jcb6>3.0.co;2-#

✦ Synopsis

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 FA/GSK-3a) 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 / G S K -~~ was found to be completed blocked. In sharp contrast, when cells were first treated with 1 pM TPA at 37°C for 24 h or with 5 pM sphingosine at 37°C for 30 min to down-regulate cellular PKC, the heat induction on kinase FA/CSK-3a was found to be reversely promoted up to -250% of control level, demonstrating that kinase F A / G S K -~~ may not represent a constitutively active/mitogeninactivated 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 FA/GSK-3a in A431 cells, suggesting that phosphorylation/dephosphorylation mechanisms are involved in the regulation of the heat-shock induction of kinase FA/GSK-3a, 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.