HEAT-STRESS INDUCES TYROSINE PHOSPHORYLATION ACTIVATION OF KINASE FA/GSK-3-ALPHA (A HUMAN CARCINOMA DEDIFFERENTIATION MODULATOR) IN A431 CELLS/

Exposure of A431 cells to a rapid temperature increase from 37 degrees to 46 degrees C could induce an increased expression (similar to 200% of control) and tyrosine phosphorylation/activation (similar to 300% of control) of protein kinase FA/glycogen synthase kinase-3 alpha (kin ase FA/GSK-3 alpha) in a time-dependent manner, as demonstrated by an anti-kinase FA/GSK-3 alpha immunoprecipitate kinase assay and by immun oblotting analysis with anti-kinase FA/GSK-3 alpha and antiphosphotyro sine antibodies. The heat induction on the increased expression of kin ase FA/GSK-3 alpha could be blocked by actinomycin D but not by genist ein. In contrast, the heat induction on tyrosine phosphorylation/activ ation of kinase FA/GSK-3 alpha could be blocked by genistein or protei n tyrosine phosphatase, indicating that heat stress induces a dual con trol mechanism, namely, protein expression and subsequent tyrosine pho sphorylation to cause cellular activation of kinase FA/GSK-3 alpha. Ta ken together, the results provide initial evidence that kinase FA/GSK- 3 alpha represents a newly described heat stress-inducible protein sub jected to tyrosine phosphorylation/activation, representing a new mode of signal transduction for the regulation of this human carcinoma ded ifferentiation modulator and a new mode of heat induction on cascade a ctivation of a protein kinase. (C) 1997 Wiley-Liss, Inc.