OLIGODENDROGLIAL SURVIVAL FACTORS, PDGF-AA AND CNTF, ACTIVATE SIMILARJAK STAT SIGNALING PATHWAYS/

Platelet-derived growth factor (PDGF) and ciliary neurotrophic factor (CNTF) have pleiotropic actions on many cell types. In the presence of these factors, oligodendroglia respond by enhanced survival when depr ived of trophic factors or in the presence of the cytotoxic cytokine, tumor necrosis factor-alpha (TNF-alpha). To determine whether these tw o oligodendroglial survival factors converge in their signaling cascad es, we examined their JAR/STAT pathways in enriched oligodendrocyte (O L) progenitors and in the progenitor OL cell line, central glia-4 (CG- 4), Cytokine pathways such as JAWSTAT have been characterized extensiv ely in hematopoietic cells; however, it is increasingly evident that t he same cytokines that play a role in hematopoiesis also play a role d uring development and injury of the central nervous system. This is th e first study that clearly defines the presence and activation of JAWS TAT proteins in OL progenitors and compares the signal transduction pa thway of two well-known oligodendroglial survival factors. In this stu dy, we report that PDGF- and CNTF-induced OL progenitors responded wit h a rapid tyrosine phosphorylation of JAK1, JAK2, STAT1 alpha/beta, an d STAT3, We feel that these identified JAWSTAT signaling molecules pla y a large role in the cellular response to these factors. Because both PDGF and CNTF enhance OL progenitor survival, these JAK/STATs may pla y a role in regulating this important cellular process. J. Neurosci. R es. 54:191-205, 1998. (C) 1998 Wiley-Liss, Inc.