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Titolo:
Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAP kinase cascade
Autore:
Avruch, J; Khokhlatchev, A; Kyriakis, JM; Luo, ZJ; Tzivion, G; Vavvas, D; Zhang, XF;
Indirizzi:
Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 bet Unit, Boston, MA 02114 USA Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Med Serv, Boston, MA 02114 USA Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Biol Mol, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA Harvard Univ BostonMA USA 02114 Sch Med, Dept Med, Boston, MA 02114 USA Boston Med Ctr, Boston, MA 02118 USA Boston Med Ctr Boston MA USA 02118Boston Med Ctr, Boston, MA 02118 USA Boston Univ, Sch Med, Boston, MA 02118 USA Boston Univ Boston MA USA 02118 oston Univ, Sch Med, Boston, MA 02118 USA
Titolo Testata:
RECENT PROGRESS IN HORMONE RESEARCH, VOL 56
, volume: 56, anno: 2001,
pagine: 127 - 155
SICI:
0079-9963(2001)56:<127:RAOTRK>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYSTEINE-RICH DOMAIN; RIBOSOMAL-PROTEIN S6; SIGNAL-TRANSDUCTION PATHWAY; GTP-BINDING PROTEIN; H-4 HEPATOMA-CELLS; GROWTH-FACTOR; B-RAF; PLASMA-MEMBRANE; IN-VIVO; HA-RAS;
Tipo documento:
Review
Natura:
Collana
Settore Disciplinare:
Clinical Medicine
Citazioni:
141
Recensione:
Indirizzi per estratti:
Indirizzo: Avruch, J Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Boston, MA 02114 USA
Citazione:
J. Avruch et al., "Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAP kinase cascade", REC PROG H, 56, 2001, pp. 127-155

Abstract

A continuing focus of our work has been an effort to understand the signaltransduction pathways through which insulin achieves its cellular actions. In the mid-1970s, we and others observed that insulin promoted an increasein Ser/Thr phosphorylation of a subset of cellular proteins. This finding was unanticipated, inasmuch as nearly all of the actions of insulin then known appeared to result from protein dephosphorylation. In fact, nearly 15 years elapsed before any physiologic response to insulin attributable to stimulated (Ser/Thr) phosphorylation was established. Nevertheless, based on the hypothesis that insulin-stimulated Ser/Thr phosphorylation reflected theactivation of protein (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and purify these putative, insulin-responsive protein(Ser/Thr) kinases. Our effort was based on the presumption that an understanding of the mechanism for their activation would provide an entry into the biochemical reactions through which the insulin receptor activated its downstream effecters. To a degree that, in retrospect, is surprising, this goal was accomplished, much in the way originally envisioned, it is now well known that receptor tyrosine kinases (RTKs) recruit a large network of protein (Ser/Thr) kinases to execute their cellular programs. The first of these insulin-activated protein kinase networks to be fully elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. This pathway is a central effector of cellular differentiation in development; moreover, its inappropriate and continuous activation provides a potent promitogenic force and is a very common occurrence in human cancers. Conversely, this pathway contributes minimally, if at all, to insulin's program of metabolic regulation. Nevertheless, the importance of the Ras-MAPK pathway in metazoan biology and human malignancies has impelled us to an ongoing analysis of the functions and regulation of Pas and Raf. This chapter will summarize brieflythe way in which work from this and other laboratories on insulin signaling led to the discovery of the mammalian MAP kinase cascade and, in turn, tothe identification of unique role of the Raf kinases in RTK activation of this protein (SerTThr) kinase cascade. We will then review in more detail current understanding of the biochemical mechanism through which the Ras proto-oncogene, in collaboration with the 14-3-3 protein and other protein kinases, initiates activation of the Raf kinase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 01:40:54