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001-es BibID:	BIBFORM035749
Első szerző:	Chan, Betty
Cím:	SAP couples Fyn to SLAM immune receptors / Chan Betty, Lanyi Arpad, Song Hyun Kyu, Griesbach Jan, Simarro-Grande Maria, Poy Florence, Howie Duncan, Sumegi Janos, Terhorst Cox, Eck Michael J.
Dátum:	2003
ISSN:	1465-7392
Megjegyzések:	SAP (SLAM-associated protein) is a small lymphocyte-specific signalling molecule that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP). Consistent with its single src homology 2 (SH2) domain architecture and unusually high affinity for SLAM (also called CD150), SAP has been suggested to function by blocking binding of SHP-2 or other SH2-containing signalling proteins to SLAM receptors. Additionally, SAP has recently been shown to be required for recruitment and activation of the Src-family kinase FynT after SLAM ligation. This signalling 'adaptor' function has been difficult to conceptualize, because unlike typical SH2-adaptor proteins, SAP contains only a single SH2 domain and lacks other recognized protein interaction domains or motifs. Here, we show that the SAP SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM. The crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex reveals that SAP binds the FynT SH3 domain through a surface-surface interaction that does not involve canonical SH3 or SH2 binding interactions. The observed mode of binding to the Fyn-SH3 domain is expected to preclude the auto-inhibited conformation of Fyn, thereby promoting activation of the kinase after recruitment. These findings broaden our understanding of the functional repertoire of SH3 and SH2 domains.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Nature Cell Biology. - 5 : 2 (2003), p. 155-160. -
További szerzők:	Lányi Árpád (1962-) (biológus, immunológus) Song, Hyun Kyu Griesbach, Jan Simarro-Grande, Maria Poy, Florence Howie, Duncan Sümegi János Terhorst, Cox Eck, Michael J.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM065580
Első szerző:	Morra, Massimo
Cím:	Characterization of SH2D1A Missense Mutations Identified in X-linked Lymphoproliferative Disease Patients / Massimo Morra, Maria Simarro-Grande, Margarita Martin, Alice Siau-In Chen, Arpad Lanyi, Olin Silander, Silvia Calpe, Jack Davis, Tony Pawson, Michael J. Eck, Janos Sumegi, Pablo Engel, Shun-Cheng Li, Cox Terhorsta
Dátum:	2001
ISSN:	0021-9258 1083-351X
Megjegyzések:	X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP disease gene product SH2D1A (SAP) interacts via its SH2 domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation. Here we analyze the effect of SH2D1A protein missense mutations identified in 10 XLP families. Two sets of mutants were found: (i) mutants with a marked decreased protein half-life (e.g. Y7C, S28R, Q99P, P101L, V102G, and X129R) and (ii) mutants with structural changes that differently affect the interaction with the four receptors. In the second group, mutations that disrupt the interaction between the SH2D1A hydrophobic cleft and Val +3 of its binding motif (e.g. T68I) and mutations that interfere with the SH2D1A phosphotyrosine-binding pocket (e.g. C42W) abrogated SH2D1A binding to all four receptors. Surprisingly, a mutation in SH2D1A able to interfere with Thr -2 of the CD150 binding motif (mutant T53I) severely impaired non-phosphotyrosine interactions while preserving unaffected the binding of SH2D1A to phosphorylated CD150. Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells. Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal Of Biological Chemistry 276 : 39 (2001), p. 36809-36816. -
További szerzők:	Simarro-Grande, Maria Martin, Margarita Chen, Alice Siau-In Lányi Árpád (1962-) (biológus, immunológus) Silander, Olin Calpe, Silvia Davis, Jack Pawson, Tony Eck, Michael J. Sümegi János Engel, Pablo Li, Shun-Cheng Terhorst, Cox
Pályázati támogatás:	PO1-AI-35714 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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