title: The Protein Tyrosine Phosphatase MEG2 Regulates the Transport and Signal Transduction of Tropomyosin Receptor Kinase A.
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.
authors.affiliation: From the Key Laboratory of Biopesticide and Chemical Biology, College of Plant Protection, Fujian Agriculture and Forestry University, 350002 Fuzhou, China.|the Departments of Biochemistry and Molecular Biology.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: the Departments of Biochemistry and Molecular Biology.
authors.forename: M Caleb
authors.initials: MC
authors.lastname: Marlin
authors.affiliation: the Departments of Biochemistry and Molecular Biology.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Cell Biology, and.
authors.forename: Mohiuddin
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Reynolds Oklahoma Center on Aging, and.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Ashpole
authors.affiliation: Reynolds Oklahoma Center on Aging, and.
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.affiliation: Pathology.|Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: the Departments of Biochemistry and Molecular Biology, guangpu-li@ouhsc.edu.|Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Guangpu
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D051379:Mice; D016501:Neurites / Q000201:enzymology*; D016716:PC12 Cells; D021381:Protein Transport / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020917:Receptor, trkA; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C507735:Ptpn9 protein, mouse
keywords: PTP-MEG2; PTPN9; TrkA; autophosphorylation; membrane trafficking; neuron; receptor tyrosine kinase; tyrosine-protein phosphatase (tyrosine phosphatase)