Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
THIOPHOSPHORYLATED SUBSTRATE-ANALOGS ARE POTENT ACTIVE-SITE-DIRECTED INHIBITORS OF PROTEIN-TYROSINE PHOSPHATASES
Autore:
HIRIYANNA KT; BAEDKE D; BAEK KH; FORNEY BA; KORDIYAK G; INGEBRITSEN TS;
Indirizzi:
IOWA STATE UNIV SCI & TECHNOL,DEPT ZOOL & GENET AMES IA 50011
Titolo Testata:
Analytical biochemistry
fascicolo: 1, volume: 223, anno: 1994,
pagine: 51 - 58
SICI:
0003-2697(1994)223:1<51:TSAPAI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOPLASMIC DOMAIN; HUMAN-PLACENTA; PURIFICATION; EXPRESSION; KINASE; SPECIFICITY; RESIDUES; PEPTIDES; CLONING; SUBUNIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
K.T. Hiriyanna et al., "THIOPHOSPHORYLATED SUBSTRATE-ANALOGS ARE POTENT ACTIVE-SITE-DIRECTED INHIBITORS OF PROTEIN-TYROSINE PHOSPHATASES", Analytical biochemistry, 223(1), 1994, pp. 51-58

Abstract

Thiophosphotyrosyl protein and peptide substrate analogs were found to be potent and specific protein-tyrosine phosphatase inhibitors with IC(50)s in the range of 0.2-30 mu M. The analogs were based on highly reactive substrates and included thiophosphotyrosyl forms of reduced carboxamidomethylated and maleylated lysozyme and peptides based on tyrosine phosphorylation sites of lysozyme, alpha(s2)-casein, and platelet-derived growth factor receptor. These analogs inhibited protein-tyrosine phosphatases from both the intracellular and transmembrane classes and from a variety of species ranging from a prokaryote (Yersinia enterolitica) to man. The extent of inhibition of phosphatase activity by a given analog varied with the phosphatase species. In contrast, protein kinases and protein-serine/threonine phosphatases were not significantly affected by these analogs. The mechanism of inhibition was investigated using rat brain protein-tyrosine phosphatase-1 as a prototype. These studies indicated that the inhibition was rapid and reversible and was competitive in nature. The K-i for inhibition by various thiophosphotyrosyl analogs was generally proportional to the apparent K-mfor the corresponding phosphorylated substrates. Unphosphorylated substrate molecules were generally much weaker inhibitors than the corresponding thiophosphotyrosyl substrate analogs. Taken together these results point to an active site-directed mechanism for inhibition. These specific inhibitory probes could be used to study substrate binding mechanisms as well as physiological roles of various protein-tyrosine phosphatases. (C) 1994 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 03:03:44