Distinct localization of SAPK isoforms in neurons of adult mouse brain implies multiple signaling modes of SAPK pathway

Various cellular and environmental stresses lead to the activation of stres s-activated protein kinase (SAPK), which is also referred to as c-Jun N-ter minal kinase (JNK). In mammals, multiple SAPK isoforms, encoded by three in dependent genes, were identified. To gain insight into the roles of SAPK pa thway in adult mouse brain, detailed expression patterns of three SAPK isof orms in brain were examined by using immunohistochemical and cell biologica l analyses. SAPK beta was heavily expressed in almost all regions of brain as previously reported. Interestingly, SAPK gamma was also widely expressed at high levels. SAPK gamma expression was generally overlapped with SAPK b eta although there were some exceptions such as in hippocampus, where SAPK gamma was restricted to CA3 and CA4 regions while SAPK beta was evenly expr essed. SAPK alpha was widely expressed, but at low levels. It is particular ly intriguing to note the differential subcellular localization of SAPK iso forms in neurons. In brain of normally reared mice, SAPK beta was identifie d in nucleus as well as in cytoplasm of neurons, while SAPK gamma was detec ted mainly in cytoplasm and dendrites. Biochemical and immunological analys es revealed extraordinarily high basal activities of all SAPK isoforms in b rain compared to peripheral organs, indicating that SAPK pathway may play a role in normal brain physiology. In addition, differential regional and su bcellular localizations of SAPK isoforms allow us to speculate multiple sig naling modes for SAPK activation in brain. (C) 1999 Elsevier Science B.V. A ll rights reserved.