Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
EMBO J
1999 Jan 04;181:109-18. doi: 10.1093/emboj/18.1.109.
Show Gene links
Show Anatomy links
Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity.
Tsai W
,
Morielli AD
,
Cachero TG
,
Peralta EG
.
???displayArticle.abstract???
The phosphorylation state of a given tyrosine residue is determined by both protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) activities. However, little is known about the functional interaction of these opposing activities at the level of an identified effector molecule. G protein-coupled receptors (GPCRs), including the m1 muscarinic acetylcholine receptor (mAChR), regulate a tyrosine kinase activity that phosphorylates and suppresses current generated by the Kv1.2 potassium channel. We examined the possibility that PTPs also participate in this signaling pathway since the tyrosine phosphatase inhibitor vanadate increases the extent of both Kv1.2 phosphorylation and suppression. We show that an endogenous transmembrane tyrosine phosphatase, receptor tyrosine phosphatase alpha (RPTPalpha), becomes tyrosine phosphorylated and co-immunoprecipitates with Kv1.2 in a manner dependent on m1 receptor activation. The N- and C-termini of Kv1.2 are shown to bind RPTPalpha in vitro. Overexpression of RPTPalpha in Xenopus oocytes increases resting Kv1.2 current. Biochemical and electrophysiological analysis reveals that recruiting RPTPalpha to Kv1.2 functionally reverses the tyrosine kinase-induced phosphorylation and suppression of Kv1.2 current in mammalian cells. Taken together, these results identify RPTPalpha as a new target of m1 mAChR signaling and reveal a novel regulatory mechanism whereby GPCR-mediated suppression of a potassium channel depends on the coordinate and parallel regulation of PTK and PTP activities.
Ali,
Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells.
1997, Pubmed
Ali,
Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells.
1997,
Pubmed
Bennett,
Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
1994,
Pubmed
Berstein,
Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-beta 1.
1992,
Pubmed
Bilwes,
Structural basis for inhibition of receptor protein-tyrosine phosphatase-alpha by dimerization.
1996,
Pubmed
Cachero,
The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel.
1998,
Pubmed
,
Xenbase
Cantley,
Oncogenes and signal transduction.
1991,
Pubmed
Catarsi,
Requirement for tyrosine phosphatase during serotonergic neuromodulation by protein kinase C.
1997,
Pubmed
Daub,
Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors.
1996,
Pubmed
Daum,
Multiple forms of the human tyrosine phosphatase RPTP alpha. Isozymes and differences in glycosylation.
1994,
Pubmed
den Hertog,
Stimulation of receptor protein-tyrosine phosphatase alpha activity and phosphorylation by phorbol ester.
1995,
Pubmed
den Hertog,
Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo.
1994,
Pubmed
Felsch,
Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor.
1998,
Pubmed
Grieco,
An improved procedure for the purification of protein fused with glutathione S-transferase.
1992,
Pubmed
Holmes,
Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain.
1996,
Pubmed
Hopfield,
Functional modulation of the nicotinic acetylcholine receptor by tyrosine phosphorylation.
1988,
Pubmed
Huang,
Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor.
1993,
Pubmed
,
Xenbase
Hunter,
Protein-tyrosine kinases.
1985,
Pubmed
Jayaraman,
Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation.
1996,
Pubmed
Lechleiter,
Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes.
1990,
Pubmed
,
Xenbase
Lechleiter,
Subcellular patterns of calcium release determined by G protein-specific residues of muscarinic receptors.
1991,
Pubmed
,
Xenbase
Lev,
Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions.
1995,
Pubmed
Lhoták,
Characterization of elk, a brain-specific receptor tyrosine kinase.
1991,
Pubmed
Li,
A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.
1994,
Pubmed
Møller,
Selective down-regulation of the insulin receptor signal by protein-tyrosine phosphatases alpha and epsilon.
1995,
Pubmed
Neel,
Protein tyrosine phosphatases in signal transduction.
1997,
Pubmed
Newton,
Protein kinase C: structure, function, and regulation.
1995,
Pubmed
Paulmichl,
Cloning and expression of a rat cardiac delayed rectifier potassium channel.
1991,
Pubmed
,
Xenbase
Pawson,
Protein modules and signalling networks.
1995,
Pubmed
Peralta,
Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes.
1988,
Pubmed
Pulido,
The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1.
1995,
Pubmed
Sap,
Cloning and expression of a widely expressed receptor tyrosine phosphatase.
1990,
Pubmed
Serra-Pagès,
The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions.
1995,
Pubmed
Stein-Gerlach,
Protein-tyrosine phosphatase 1D modulates its own state of tyrosine phosphorylation.
1995,
Pubmed
Stover,
Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases.
1994,
Pubmed
Su,
Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and associated with the adaptor protein Grb2.
1994,
Pubmed
Toullec,
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
1991,
Pubmed
Tracy,
The receptor-like protein-tyrosine phosphatase, RPTP alpha, is phosphorylated by protein kinase C on two serines close to the inner face of the plasma membrane.
1995,
Pubmed
Tsai,
The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate ion channel activity.
1997,
Pubmed
Ullrich,
Signal transduction by receptors with tyrosine kinase activity.
1990,
Pubmed
Vogel,
Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation.
1993,
Pubmed
Wang,
Regulation of NMDA receptors by tyrosine kinases and phosphatases.
1994,
Pubmed
Wilson,
Mode-switching of a voltage-gated cation channel is mediated by a protein kinase A-regulated tyrosine phosphatase.
1993,
Pubmed
Zheng,
Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase.
1992,
Pubmed
