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Titolo:
Structure of the Tie2 RTK domain: Self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail
Autore:
Shewchuk, LM; Hassell, AM; Ellis, B; Holmes, WD; Davis, R; Horne, EL; Kadwell, SH; McKee, DD; Moore, JT;
Indirizzi:
Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA Glaxo Wellcome Inc Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Titolo Testata:
STRUCTURE
fascicolo: 11, volume: 8, anno: 2000,
pagine: 1105 - 1113
SICI:
0969-2126(20001115)8:11<1105:SOTTRD>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR TYROSINE KINASE; ENDOTHELIAL GROWTH-FACTOR; CRYSTAL-STRUCTURE; VENOUS MALFORMATIONS; VASCULAR DEVELOPMENT; SIGNALING PATHWAYS; INSULIN-RECEPTOR; PROTEIN-KINASES; ANGIOGENESIS; ANGIOPOIETIN-1;
Keywords:
tyrosine kinase; Tek; angiogenesis; X-ray structure; kinase insert domain; signal transduction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Shewchuk, LM Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA Glaxo Wellcome Inc Res Triangle Pk NC USA 27709 NC 27709 USA
Citazione:
L.M. Shewchuk et al., "Structure of the Tie2 RTK domain: Self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail", STRUCTURE, 8(11), 2000, pp. 1105-1113

Abstract

Background: Angiogenesis, the formation of new vessels from the existing vasculature, is a critical process during early development as well as in a number of disease processes. Tie2 (also known as Tek) is an endothelium-specific receptor tyrosine kinase involved in both angiogenesis and vasculature maintenance. Results: We have determined the crystal structure of the Tie2 kinase domain to 2.2 Angstrom resolution. The structure contains the catalytic core, the kinase insert domain (KID), and the C-terminal tail. The overall fold is similar to that observed in other serine/threonine and tyrosine kinase structures; however, several unique features distinguish the Tie2 structure from those of other kinases. The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an "activated-like" conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated. Conclusion: Regulation of the kinase activity of Tie2 is a complex process. Conformational changes in the nucleotide binding loop, activation loop, Chelix, and the C-terminal tail are required for ATP and substrate binding.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 03:13:51