Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38alpha and its splice isoform Mxi2.
The p38 family of mitogen-activated protein kinases is composed of several isoforms. Mxi2 is a splicing variant of p38alpha that harbors a unique carboxy-terminus. Here we show that this sole divergence results in remarkable differences between Mxi2 and p38alpha. Mxi2 is distinctively activated by stress stimuli and potently activated by mitogens. Mxi2 affinity for bona fide p38 substrates is remarkably diminished and Mxi2 activity is largely unaffected by the phosphatase CL100. Also, Mxi2 sensitivity to inhibition by SB203580 is greatly reduced. Interestingly, we show that the p38 C-terminus is involved in conferring sensitivity to this compound. Overall, our results point to the p38 carboxy-terminus as a key determinant of the biochemical properties of this family of kinases.
Sanz
V
V
Unidad de Biología Molecular del Cáncer, Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Arozarena
I
I
Crespo
P
P
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
D018797:Cell Cycle Proteins; D007093:Imidazoles; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases; C093642:SB 203580