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 phosp horylating c-Jun on serines 63 and 73. The molecular weight of this ki nase 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/re perfusion 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, revea led the phosphorylation (activation) of a 37 kD protein in response to hypoxia. The 37 kD protein in RPTE cells is phosphorylated by other s tress 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 result s of this study have led to the identification of a potentially novel kinase closely related to JNK but showing a distinct pattern of activa tion. (C) 1998 Academic Press.