期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 46, 页码 23895-23905出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.728550
关键词
autophosphorylation; membrane trafficking; neuron; receptor tyrosine kinase; tyrosine-protein phosphatase (tyrosine phosphatase); PTP-MEG2; PTPN9; TrkA
资金
- Oklahoma Center for the Advancement of Science and Technology (OCAST) [HR15-089]
- National Institutes of Health [R01GM074692]
Protein tyrosine phosphatase MEG2 (PTP-MEG2) is a unique nonreceptor tyrosine phosphatase associated with transport vesicles, where it facilitates membrane trafficking by dephosphorylation of the N-ethylmaleimide-sensitive fusion factor. In this study, we identify the neurotrophin receptor TrkA as a novel cargo whose transport to the cell surface requires PTP-MEG2 activity. In addition, TrkA is also a novel substrate of PTP-MEG2, which dephosphorylates both Tyr-490 and Tyr-674/Tyr-675 of TrkA. As a result, overexpression of PTP-MEG2 down-regulates NGF/TrkA signaling and blocks neurite outgrowth and differentiation in PC12 cells and cortical neurons.
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