ISSN:
1573-4943
Keywords:
Proline-directed protein kinase FA/GSK-3α
;
protein kinase C
;
sphingosine
;
TPA
;
signal transduction
;
tyrosine phosphorylation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract When serum-starved A431 cells were treated with 200 nM phorbol ester TPA for 15 min, the cellular activity of protein kinase FA/glycogen synthase kinase-3α (kinase FA/GSK-3α) could be decreased to ~25% of control. Conversely, when treated with 1 μM TPA for 24 hr, the activity could be reversibly increased to ~200% of Control. The naturally occurring protein kinase C (PKC) inhibitor sphingosine at a concentration of 27 μM could also induce activation of kinase FA/GSK-3α to ~200% of control within 60 min. Further, when cells were chronically treated with 1 μM TPA for 24 hr and then with 27 μM sphingosine for 60 min, the activity of kinase FA/GSK-3α could only be increased to ~200% of control. Furthermore, when cells were pretreated with sphingosine and then acutely treated with TPA, the acute TPA effect on kinase FA/GSK-3α activity could be abolished by genistein or tyrosine phosphorylation, which could be blocked by genistein or tyrosine phosphatase, but could be reversed by orthovanadate. Taken together, the results demonstrate that TPA/sphingosine induce tyrosine phosphorylation and concurrent activation of kinase FA/GSK-3α in a common signalling pathway. Since TPA and sphingosine are potent PKC modulators, the results further suggest a potential role of PKC in modulating tyrosine phosphorylation/activation of kinase FA/GSK-3α. Kinetic studies on seven subtypes of PKC further demonstrate a specific involvement of PKC∈ in this tyrosine phosphorylation/activation process. This provides a new mode of signal transduction between these two important serine/threonine kinases in cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1022582312954
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