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001-es BibID:	BIBFORM054319
035-os BibID:	PMID: 11453982
Első szerző:	Koncz Gábor (biológus, immunológus)
Cím:	Co-clustering of Fcγ and B cell receptors induces dephosphorylation of the Grb2-associated binder 1 docking protein / Gábor Koncz, Gábor K. Tóth, Gyöngyi Bökönyi, György Kéri, Israel Pecht, David Medgyesi, János Gergely, Gabriella Sármay
Dátum:	2001
ISSN:	0014-2956 1432-1033
Megjegyzések:	The immunoreceptor tyrosine-based inhibitory motif (ITIM) of human type Ilb Fc gamma receptor (Fc gamma RIIb) is phosphorylated on its tyrosine upon co-clustering with the B cell receptor (BCR). The phosphorylated ITIM (p-ITIM) binds to the SH2 domains of polyphosphoinositol 5-phosphatase (SHIP) and the tyrosine phosphatase, SHP-2. We investigated the involvement of the molecular complex composed of the phosphorylated SHIP and Fc gamma RIIb in the activation of SHP-2. As a model compound, we synthesized a bisphosphopeptide, combining the sequences of p-ITIM and the N-terminal tyrosine phosphorylated motif of SHIP with a flexible spacer. This compound bound to the recombinant SH2 domains of SHP-2 with high affinity and activated the phosphatase in an in vitro assay. These data suggest that the phosphorylated Fc gamma RII-SHIP complexes formed in the intact cells may also activate SHP-2. Grb2-associated binder 1 (Gab1) is a multisite docking protein, which becomes tyrosine-phosphorylated in response to various types of signaling, including BCR. In turn it binds to the SH2 domains of SHP-2, SHIP and the p85 subunit of phosphatidyl inositol 3-kinase (PtdIns3-K) and may regulate their activity. Gab1 is a potential substrate of SHP-2, thus its binding to Fc gamma RIIb may modify the Gab1-bound signaling complex. We show here that Gab1 is part of the multiprotein complex assembled by Fc gamma RIIb upon its co-clustering with BCR. Gab1 may recruit SH2 domain-containing molecules to the phosphorylated Fc gamma RIIb. SHP-2, activated upon the binding to Fc gamma RIIb-SHIP complex, partially dephosphorylates Gab1, resulting in the release of PtdIns3-K and ultimately in the inhibition of downstream activation pathways in BCR/Fc gamma RIIb co-aggregated cells.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban B-lymphocytes Fc gamma receptors IIb signal transduction
Megjelenés:	European Journal of Biochemistry. - 268 : 14 (2001), p. 3898-3906. -
További szerzők:	Tóth Gábor K. Bökönyi Gyöngyi Kéri György Pecht, Israel Medgyesi Dávid Gergely János Sármay Gabriella
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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