c‐Jun N‐terminal kinase‐3 (JNK3)/stress‐activated protein kinase‐β (SAPKβ) binds and phosphorylates the neuronal microtubule regulator SCG10

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Abstract
The neuronal growth‐associated protein SCG10 is enriched in the growth cones of neurons where it destabilizes microtubules and thus contributes to the dynamic assembly and disassembly of microtubules. Since its microtubule‐destabilizing activity is regulated by phosphorylation, SCG10 may link extracellular signals to rearrangements of the neuronal cytoskeleton. To identify signal transduction pathways that may lead to SCG10 phosphorylation, we tested a series of serine–threonine‐directed protein kinases that phosphorylate SCG10 in vitro. We demonstrate that purified SCG10 can be phosphorylated by two subclasses of mitogen‐activated protein (MAP) kinases, c‐Jun N‐terminal/stress‐activated protein kinase (JNK/SAPK) and p38 MAP kinase. Moreover, SCG10 was found to bind tightly and specifically to JNK3/SAPKβ. JNK3/SAPKβ phosphorylation occurs at Ser‐62 and Ser‐73, residues that result in reduced microtubule‐destabilizing activity for SCG10. Endogenous SCG10 also undergoes increased phosphorylation in sympathetic neurons at times of JNK3/SAPKβ activation following deprivation from nerve growth factor. Together these observations indicate that activation of JNK/SAPKs provides a pathway for phosphorylation of SCG10 and control of growth cone microtubule formation following neuronal exposure to cellular stresses.