Identification of a novel stress activated kinase in kidney and heart.
We have previously described the patterns of stress kinase activation in rat kidney and heart in response to ischemia/reperfusion (Yin et al., 1997, J. Biol. Chem. 272, 19943-19950). During the course of these studies, we observed the activation of a novel kinase capable of phosphorylating c-Jun on serines 63 and 73. The molecular weight of this kinase is approximately 37 kD, significantly below the molecular weight of all previously identified Jun N-terminal kinase (JNK) isoforms. The pattern of activation of this 37 kD kinase in response to ischemia/reperfusion in both kidney and heart is distinct from that of known JNK isoforms. Western analysis of human renal proximal tubular epithelial (RPTE) cells, using a non-isoform specific phospho-JNK antibody, revealed the phosphorylation (activation) of a 37 kD protein in response to hypoxia. The 37 kD protein in RPTE cells is phosphorylated by other stress stimuli capable of activating JNK. Western analysis of tissues, using a non-isoform specific JNK antibody, identifies a cross-reactive 37 kD protein expressed in the liver, thymus and lymph node which is likely to correspond to the 37 kDa stress-activated kinase. The results of this study have led to the identification of a potentially novel kinase closely related to JNK but showing a distinct pattern of activation.
De Silva
H
H
Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, New Jersey, 07901, USA.
Cioffi
C
C
Yin
T
T
Sandhu
G
G
Webb
R L
RL
Whelan
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D007527:Isoenzymes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases