Reference - Detail
| RRC ID | 42233 |
|---|---|
| Author | Isnardi I, Lesourne R, Bruhns P, Fridman WH, Cambier JC, Daëron M. |
| Title | Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap. |
| Journal | J Biol Chem |
| Abstract |
FcgammaRIIB are low-affinity receptors for IgG that contain an immunoreceptor tyrosine-based inhibition motif (ITIM) and inhibit immunoreceptor tyrosine-based activation motif (ITAM)-dependent cell activation. When coaggregated with ITAM-bearing receptors, FcgammaRIIB become tyrosyl-phosphorylated and recruit the Src homology 2 (SH2) domain-containing inositol 5'-phosphatases SHIP1 and SHIP2, which mediate inhibition. The FcgammaRIIB ITIM was proposed to be necessary and sufficient for recruiting SHIP1/2. We show here that a second tyrosine-containing motif in the intracytoplasmic domain of FcgammaRIIB is required for SHIP1/2 to be coprecipitated with the receptor. This motif functions as a docking site for the SH2 domain-containing adapters Grb2 and Grap. These adapters interact via their C-terminal SH3 domain with SHIP1/2 to form a stable receptor-phosphatase-adapter trimolecular complex. Both Grb2 and Grap are required for an optimal coprecipitation of SHIP with FcgammaRIIB, but one adapter is sufficient for the phosphatase to coprecipitate in a detectable manner with the receptors. In addition to facilitating the recruitment of SHIPs, the second tyrosine-based motif may confer upon FcgammaRIIB the properties of scaffold proteins capable of altering the composition and stability of the signaling complexes generated following receptor engagement. |
| Volume | 279(50) |
| Pages | 51931-8 |
| Published | 2004-12-10 |
| DOI | 10.1074/jbc.M410261200 |
| PII | S0021-9258(20)67628-1 |
| PMID | 15456754 |
| MeSH | Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / metabolism* Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Cell Line Chickens GRB2 Adaptor Protein In Vitro Techniques Inositol Polyphosphate 5-Phosphatases Mice Molecular Sequence Data Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases / chemistry Phosphoric Monoester Hydrolases / metabolism* Protein Binding Receptors, IgG / chemistry* Receptors, IgG / genetics Receptors, IgG / metabolism* Recombinant Proteins / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Transfection Tyrosine / chemistry src Homology Domains |
| IF | 4.238 |
| Times Cited | 37 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | |