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Biochemical and biological characterization of a neuroendocrine‐associated phosphatase
Author(s) -
Wang JizYuh,
Lin ChiaHua,
Yang ChiHwa,
Tan TseHua,
Chen YiRong
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03852.x
Subject(s) - microbiology and biotechnology , protein kinase b , kinase , neurite , mapk/erk pathway , phosphatase , protein kinase a , nerve growth factor , p38 mitogen activated protein kinases , pi3k/akt/mtor pathway , biology , dual specificity phosphatase , phosphorylation , signal transduction , chemistry , in vitro , biochemistry , receptor
The biochemical and biological properties of a novel neuroendocrine‐associated phosphatase (NEAP) were characterized. NEAP had a sequence characteristic of a dual‐specificity phosphatase (DSP), and was preferentially expressed in neuroendocrine cells/tissues as well as in skeletal muscle and heart. Expression of NEAP was up‐regulated in nerve growth factor (NGF)‐treated, differentiated PC12 cells. NEAP was cytosolic and did not apparently have effects against extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase activated by various stimuli. Although NEAP and MAPK phosphatase (MPK)‐1 showed similar phosphatase activity towards p ‐nitro phenylphosphate ( p NPP), in contrast to MKP‐1, NEAP did not dephosphorylate JNK and p38‐MAPK in vitro . Overexpression of NEAP, but not the C152S mutant, in PC12 cells suppressed NGF‐induced phosphorylation of the p85 subunit of phosphatidylinositol 3‐kinase (PI3K) and Akt activation. Overexpression of NEAP also suppressed neurite outgrowth induced by NGF and sensitized PC12 cells to cisplatin‐induced apoptosis. Suppression of NEAP by RNA interference enhanced NGF‐induced neurite outgrowth and Akt activation. Our results indicated that, unlike other DSPs, down‐regulation of conventional MAPKs was not the major function of NEAP. Furthermore, NEAP might be involved in neuronal differentiation via regulation of the PI3K/Akt signaling.