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PMID: 9285826 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A role for the SHP-2 tyrosine phosphatase in nerve growth-induced PC12 cell differentiation.

Molecular biology of the cell ·Vol. 8 ·No. 8 ·1997-08-00 ·Pages 1575-85

Wright JH, Drueckes P, Bartoe J, Zhao Z, Shen SH, Krebs EG

Abstract

SHP-1 and SHP-2 are intracellular protein tyrosine phosphatases containing two adjacent src homology 2 domains that target these phosphatases to cell surface receptor signaling complexes and play a role in receptor signal transduction. In this report the PC12 cell system was used to investigate the potential roles of SHP-1 and SHP-2 in the induction of neuronal differentiation by nerve growth factor (NGF). By using neurite outgrowth as a marker for differentiation, the effects of transfected constructs of SHP-1 and SHP-2 were assessed. Overexpression of a catalytically inactive SHP-2, but not a catalytically inactive SHP-1, blocked NGF-stimulated neurite outgrowth. The mitogen-activated protein kinase (MAPK) signaling cascade is important for the morphological differentiation in PC12 cells, and both SHP-1 and SHP-2 have been implicated to act upstream of MAPK in other receptor signaling systems. A positive role for SHP-2 but not SHP-1 in the activation of MAPK by NGF was demonstrated by introduction of the SHP-2 phosphatase mutants along with hemagglutinin-tagged MAPK. Coexpression studies with the SHP-2 mutant along with mutant forms of MAPK kinase suggested that SHP-2 functions upstream of MAPK kinase and MAPK in NGF-induced neurite outgrowth.

MeSH Terms
Animals Cell Differentiation/physiology Enzyme Activation Gene Transfer Techniques Intracellular Signaling Peptides and Proteins Nerve Growth Factors/physiology Neurites/physiology PC12 Cells Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases/genetics,physiology Rats Transfection
Chemicals
Intracellular Signaling Peptides and Proteins Nerve Growth Factors Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases Ptpn11 protein, rat Ptpn6 protein, rat
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wright J H
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Drueckes P
Bartoe J
Zhao Z
Shen S H
Krebs E G
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.8.8.1575
Published
1997-08-00
Pages
1575-85
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC276177
Subset
IM
Grants
NIDDK NIH HHS · DK-42528 · United States
NIGMS NIH HHS · GM-42508 · United States
NHLBI NIH HHS · HL-07312 · United States
External Links
PubMed source DOI: 10.1091/mbc.8.8.1575 PMC Full Text View journal details
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