| RRC ID |
42233
|
| 著者 |
Isnardi I, Lesourne R, Bruhns P, Fridman WH, Cambier JC, Daëron M.
|
| タイトル |
Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap.
|
| ジャーナル |
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.
|
| 巻・号 |
279(50)
|
| ページ |
51931-8
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| 公開日 |
2004-12-10
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| DOI |
10.1074/jbc.M410261200
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| PII |
S0021-9258(20)67628-1
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| 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
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| 引用数 |
37
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
