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

FEBS Letters

Grenningloh, Gabriele³  Neidhart, Sybille³  Gilliéron, Corine¹  Vilbois, Francis¹  Arkinstall, Steve²  Antonsson, Bruno¹ 

[1]Serono Pharmaceutical Research Institute, chemin des Aulx 14, 1228 Plan-les-Ouates, Geneva, Switzerland

[2]Serono Reproductive Biology Institute, Randolph, MA 02368, USA

[3]Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, rue du Bugnon 9, 1005 Lausanne, Switzerland

关键词: SCG10;    Phosphorylation;    Stress-activated protein kinase;    c-Jun N-terminal kinase;    Mitogen-activated protein;    Scintillation proximity assay;    JNK/SAPK;    c-Jun N-terminal/stress-activated protein kinase;    MAP kinase;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;    MBP;    myelin basic protein;    MS;    mass spectrometry;    SPA;    scintillation proximity assay;    NGF;    nerve growth factor;   

DOI  :  10.1016/S0014-5793(01)03090-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown