Naslov
Both SH2 Domains Are Involved in Interaction of SHP-1 with the Epidermal Growth Factor Receptor but Cannot Confer Receptor-directed Activity to SHP-1/SHP-2 Chimera

Autori
Tenev, Tencho ; Keilhack, Heike ; Tomic, Sinisa ; Stoyanov, Boris ; Stein-Gerlach, Matthias ; Lammers, Reiner ; Krivtsov, Andrei V. ; Ullrich, Axel ; Böhmer, Frank-D.

Izvornik
Journal of Biological Chemistry (0021-9258) 272 (1997), 9; 5966-5973

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
protein-tyrosine phosphatases, SHP-1, EGF receptor, dephosphorylation

Sažetak
The previously demonstrated functional and physical interaction of the SH2 domain protein-tyrosine phosphatase SHP-1 withthe epidermal growth factor (EGF) receptor (Tomic, S., Greiser, U., Lammers, R., Kharitonenkov, A., Imyanitov, E., Ullrich, A., and Böhmer, F. D. (1995) J. Biol. Chem. 270, 21277-21284) was investigated with respect to the involved structural elements of SHP-1. Various mutants of SHP-1 weretransiently expressed in 293 or COS-7 cells and analyzed for their capacity to associate with immobilized autophosphorylatedEGF receptor in vitro and to dephosphorylate coexpressed EGF receptor in intact cells. Inactivating point mutation of the C-terminal SH2 domainreduced the association weakly, point mutation of the N-terminal SH2 domain reduced association strongly and the respectivedouble mutation abolished association totally. The capacity of SHP-1 to dephosphorylate coexpressed EGF receptor was impairedby all point mutations. Truncation of the N-terminal or of both SH2 domains strongly reduced or abolished association, respectively, but the truncated SHP-1 derivatives still dephosphorylated coexpressed EGF receptor effectively. Various chimeric protein-tyrosine phosphatases constructed from SHP-1 and the closely homologous SHP-2 dephosphorylated theEGF receptor when they contained the catalytic domain of SHP-1. As native SHP-2, the chimera lacked activity toward the receptorwhen they contained the catalytic domain of SHP-2, despite their capacity to associate with the receptor and to dephosphorylatean artificial phosphopeptide. We conclude that the differential interaction of SHP-1 and SHP-2 with the EGF receptor is dueto the specificity of the respective catalytic domains rather than to the specificity of the SH2 domains. Functional interactionof native SHP-1 with the EGF receptor requires association mediated by both SH2 domains.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA