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Titolo:
UCS15A, a non-kinase inhibitor of Src signal transduction
Autore:
Sharma, SV; Oneyama, C; Yamashita, Y; Nakano, H; Sugawara, K; Hamada, M; Kosaka, N; Tamaoki, T;
Indirizzi:
Kyowa Hakko Kogyo Co Ltd, Tokyo Res Labs, Machida, Tokyo 194, Japan Kyowa Hakko Kogyo Co Ltd Machida Tokyo Japan 194 achida, Tokyo 194, Japan Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Labs, Nagaizumi, Shizuoka 411, Japan Kyowa Hakko Kogyo Co Ltd Nagaizumi Shizuoka Japan 411 Shizuoka 411, Japan Natl Inst Basic Biol, Okazaki Natl Res Inst, Div Morphogenesis, Okazaki, Aichi 4448585, Japan Natl Inst Basic Biol Okazaki Aichi Japan 4448585 ki, Aichi 4448585, Japan
Titolo Testata:
ONCOGENE
fascicolo: 17, volume: 20, anno: 2001,
pagine: 2068 - 2079
SICI:
0950-9232(20010419)20:17<2068:UANIOS>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
OSTEOCLASTIC BONE-RESORPTION; PP60C-SRC PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; FOCAL ADHESION KINASE; TYROSINE KINASE; C-SRC; SH3 DOMAIN; CRYSTAL-STRUCTURE; HERBIMYCIN-A; IN-VITRO;
Keywords:
Src; UCS15A; bone resorption inhibitor; protein-protein interaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Sharma, SV Kyowa Hakko Kogyo Co Ltd, Tokyo Res Labs, 3-6-6 Asahimachi, Machida, Tokyo194, Japan Kyowa Hakko Kogyo Co Ltd 3-6-6 Asahimachi Machida Tokyo Japan 194
Citazione:
S.V. Sharma et al., "UCS15A, a non-kinase inhibitor of Src signal transduction", ONCOGENE, 20(17), 2001, pp. 2068-2079

Abstract

Src tyrosine kinase plays key roles in signal transduction following growth factor stimulation and integrin-mediated cell-substrate adhesion. Since src-signal transduction defects are implicated in a multitude of human diseases, we have sought to develop new ways to identify small molecule inhibitors using a yeast-based, activated-src over-expression system, In the present study, we describe the identification of a unique src-signal transductioninhibitor, UCS15A, UCS15A was found to inhibit the src specific tyrosine phosphorylation of numerous proteins in v-src-transformed cells, Two of these phosphoproteins were identified as bona-fide src substrates, cortactin and Sam68, UCS15A differed from conventional src-inhibitors in that it did not inhibit the tyrosine kinase activity of src, In addition, UCS15A appearedto differ from src-destabilizing agents such as herbimycin and radicicol that destabilize src by interfering with Hsp90. Our studies suggest that UCS15A exerted its src-inhibitory effects by a novel mechanism that involved disruption of protein-protein interactions mediated by src, One of the biological consequences of src-inhibition by UCS15A was its ability to inhibit the bone resorption activity of osteoclasts in vitro, These data suggest that UCS15A may inhibit the bone resorption activity of osteoclasts, not by inhibiting src tyrosine kinase activity, but by disrupting the interaction ofproteins associated with src, thereby modulating downstream events in the src signal transduction pathway.

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Documento generato il 05/12/20 alle ore 01:13:29