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J Biol Chem. 2016 Nov 11;291(46):23895-23905. Epub 2016 Sep 21.

The Protein Tyrosine Phosphatase MEG2 Regulates the Transport and Signal Transduction of Tropomyosin Receptor Kinase A.

Author information

1
From the Key Laboratory of Biopesticide and Chemical Biology, College of Plant Protection, Fujian Agriculture and Forestry University, 350002 Fuzhou, China.
2
the Departments of Biochemistry and Molecular Biology.
3
Cell Biology, and.
4
Reynolds Oklahoma Center on Aging, and.
5
Pathology.
6
Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
7
the Departments of Biochemistry and Molecular Biology, guangpu-li@ouhsc.edu.

Abstract

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.

KEYWORDS:

PTP-MEG2; PTPN9; TrkA; autophosphorylation; membrane trafficking; neuron; receptor tyrosine kinase; tyrosine-protein phosphatase (tyrosine phosphatase)

PMID:
27655914
PMCID:
PMC5104914
DOI:
10.1074/jbc.M116.728550
[Indexed for MEDLINE]
Free PMC Article

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