c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPK beta) binds and phosphorylates the neuronal microtubule regulator SCG10

The neuronal growth-associated protein SCG10 is enriched in the growth cone s of neurons where it destabilizes microtubules, and thus contributes to th e dynamic assembly and disassembly of microtubules. Since its microtubule-d estabilizing activity is regulated by phosphorylation, SCG10 may link extra cellular signals to rearrangements of the neuronal cytoskeleton. To identif y signal transduction pathways that may lead to SCG10 phosphorylation, we t ested a series of serine-threonine-directed protein kinases that phosphoryl ate SCG10 in vitro. We demonstrate that purified SCG10 can be phosphorylate d by two subclasses of mitogen-activated protein (MAP) kinases, e-Jun N-ter minal/stress-activated protein kinase (JNK/SAPK) and p38 MAP kinase. Moreov er, SCG10 was found to bind tightly and specifically to JNK3/SAPK beta. JNK 3/SAPK beta phosphorylation occurs at Ser-62 and Ser-73, residues that resu lt in reduced microtubule-destabilizing activity for SCG10. Endogenous SCG1 0 also undergoes increased phosphorylation in sympathetic neurons at times of JNK3/SAPK beta activation following deprivation from nerve growth factor . Together these observations indicate that activation of JNK/SAPKs provide s a pathway for phosphorylation of SCG10 and control of growth cone microtu bule formation following neuronal exposure to cellular stresses. (C) 2001 F ederation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.