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 (approximately 200% of control) and tyrosine phosphorylation/activation (approximately 300% of control) of protein kinase FA/ glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) in a time-dependent manner, as demonstrated by an anti-kinase FA/GSK-3 alpha immunoprecipitate kinase assay and by immunoblotting analysis with anti-kinase FA/GSK-3 alpha and anti-phosphotyrosine antibodies. The heat induction on the increased expression of kinase FA/GSK-3 alpha could be blocked by actinomycin D but not by genistein. In contrast, the heat induction on tyrosine phosphorylation/activation of kinase FA/GSK-3 alpha could be blocked by genistein or protein tyrosine phosphatase, indicating that heat stress induces a dual control mechanism, namely, protein expression and subsequent tyrosine phosphorylation to cause cellular activation of kinase FA/GSK-3 alpha. Taken together, the results provide initial evidence that kinase FA/GSK-3 alpha represents a newly described heat stress-inducible protein subjected to tyrosine phosphorylation/activation, representing a new mode of signal transduction for the regulation of this human carcinoma dedifferentiation modulator and a new mode of heat induction on cascade activation of a protein kinase.
Yang
S D
SD
Department of Life Sciences, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
Lee
S C
SC
Chang
H C
HC
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D018882:Heat Stress Disorders / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007529:Isoflavones; D004676:Myelin Basic Protein; D003609:Dactinomycin; D019000:Phosphotyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3