A role for the SHP-2 tyrosine phosphatase in nerve growth-induced PC12 cell differentiation.
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.
Wright
J H
JH
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Drueckes
P
P
Bartoe
J
J
Zhao
Z
Z
Shen
S H
SH
Krebs
E G
EG
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004789:Enzyme Activation; D018014:Gene Transfer Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors / Q000502:physiology; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014162:Transfection
D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat