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Titolo:
The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells
Autore:
Yamashita, H; Avraham, S; Jiang, SX; Dikic, I; Avraham, H;
Indirizzi:
Beth Israel Deaconess Med Ctr, Div Expt Med, Harvard Inst Med, Harvard MedSch, Boston, MA 02115 USA Beth Israel Deaconess Med Ctr Boston MA USA 02115 h, Boston, MA 02115 USA Biomed Ctr, Ludwig Inst Canc Res, S-75124 Uppsala, Sweden Biomed Ctr Uppsala Sweden S-75124 Inst Canc Res, S-75124 Uppsala, Sweden
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 21, volume: 274, anno: 1999,
pagine: 15059 - 15065
SICI:
0021-9258(19990521)274:21<15059:TCHKAW>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; SIGNAL-TRANSDUCTION PATHWAYS; FAMILY TYROSINE KINASES; BREAST-CANCER CELLS; NEURONAL DIFFERENTIATION; PROTOONCOGENE PRODUCT; MOLECULAR-CLONING; BINDING-SITES; C-KIT; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Avraham, H Beth Israel Deaconess Med Ctr, Div Expt Med, Harvard Inst Med, Harvard MedSch, 4 Blackfan Circle, Boston, MA 02115 USA Beth Israel Deaconess Med Ctr 4 Blackfan Circle Boston MA USA 02115
Citazione:
H. Yamashita et al., "The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells", J BIOL CHEM, 274(21), 1999, pp. 15059-15065

Abstract

Csk homologous kinase (CHK), a member of the Csk regulatory tyrosine kinase family, is expressed primarily in brain and hematopoietic cells. The roleof CHK in the nervous system is as yet unknown. Using PC12 cells as a model system of neuronal cells, we show that CHK participates in signaling mediated by TrkA receptors, CHK was found to be associated with tyrosine phosphorylated TrkA receptors in PC12 cells upon stimulation with NGF. Binding assays and far Western blotting analysis, using glutathione S-transferase fusion proteins containing the Src homology 2 (SH2) and SH3 domains of CHK, demonstrate that the SH2 domain of CHK binds directly to the tyrosine-phosphorylated TrkA receptors. Site-directed mutagenesis of TrkA cDNA, as well as phosphopeptide inhibition of the in vitro interaction of the CHK-SH2 domainor native CHK with TrkA receptors, indicated that the residue Tyr-785 on TrkA is required for its binding to the CHK-SH2 domain upon NGF stimulation. In addition, overexpression of CHK resulted in enhanced activation of the mitogen-activated protein kinase pathway upon NGF stimulation, and microinjection of anti-CHK antibodies, but not anti-Csk antibodies, inhibited neurite outgrowth of PC12 cells in response to NGF. Thus, CHK is a novel signaling molecule that participates in TrkA signaling, associates directly with TrkA receptors upon NGF stimulation, and is involved in neurite outgrowth ofPC12 cells in response to NGF.

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Documento generato il 11/07/20 alle ore 04:45:51