The Negative Signaling Molecule SH2 Domain-containing Inositol-Polyphosphate 5-Phosphatase (SHIP) Binds to the Tyrosine-phosphorylated β Subunit of the High Affinity IgE Receptor*
The Negative Signaling Molecule SH2 Domain-containing Inositol-Polyphosphate 5-Phosphatase (SHIP) Binds to the Tyrosine-phosphorylated β Subunit of the High Affinity IgE Receptor*
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含有 SH2 结构域的负信号分子肌醇聚磷酸 5-磷酸酶 (SHIP) 与高亲和力 IgE 受体的酪氨酸磷酸化 β 亚基结合*
DOI：
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发表时间：
1997
影响因子：
4.8
通讯作者：
R. Siraganian
中科院分区：
文献类型：
--
作者：
Teruaki Kimura;H. Sakamoto;E. Appella;R. Siraganian
含SH 2结构域的肌醇-多磷酸5-磷酸酶SHIP与FcγRIIB结合，并负调节B细胞和肥大细胞功能。我们报道了在大鼠嗜碱性白血病RBL-2 H3细胞中，高亲和力IgE受体（FcεRI）聚集后SHIP被酪氨酸磷酸化。SHIP的酪氨酸磷酸化是受体聚集后的早期事件，并且存在于蛋白酪氨酸激酶Syk缺陷的细胞中。此外，它不是继发于细胞内钙的增加或蛋白激酶C的激活。SHIP通过基于高亲和力IgE受体的β亚基而非γ亚基的免疫受体酪氨酸基活化基序（ITAM）的固定化磷酸化合成肽沉淀。SHIP的酪氨酸磷酸化及其与FcεRI的酪氨酸磷酸化β亚基的结合可能在下调肥大细胞受体介导的信号转导中发挥重要作用。因此，尽管活化分子Syk与γ亚基ITAM结合，β亚基ITAM与负信号分子SHIP结合。因此，不像B细胞中抗原受体和辅助受体（如FcγRIIB或CD 22）各自招募具有相反作用的分子，FcεRI含有招募激活和抑制信号转导的分子的亚基。
The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates with FcγRIIB and negatively regulates both B-cell and mast cell function. We report here that SHIP was tyrosine-phosphorylated after high affinity IgE receptor (FcεRI) aggregation in rat basophilic leukemia RBL-2H3 cells. The tyrosine phosphorylation of SHIP was an early event after receptor aggregation and was present in cells deficient in the protein-tyrosine kinase Syk. Furthermore it was not secondary to the increase of intracellular calcium or the activation of protein kinase C. SHIP was precipitated by immobilized phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based activation motif (ITAM) of the β but not the γ subunit of the high affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with the tyrosine-phosphorylated β subunit of FcεRI could play an important role in down-regulating receptor-mediated signal transduction in mast cells. Thus, whereas the activation molecule Syk associates with the γ subunit ITAM, the β subunit ITAM binds the negative signaling molecule SHIP. Therefore, unlike B cells where the antigen receptor and coreceptors such as FcγRIIB or CD22 each recruits molecules with opposite effects, the FcεRI contains subunits which recruit molecules that activate and inhibit signal transduction.
DOI：
10.1073/pnas.93.4.1689
发表时间：
1996-02-20
影响因子：
11.1
作者：
Damen, JE;Liu, L;Krystal, G
通讯作者：
Krystal, G
影响因子：
56.9
作者：
KAVANAUGH, WM;WILLIAMS, LT
通讯作者：
WILLIAMS, LT
影响因子：
4.4
作者：
George Chacko;S. Tridandapani;J. Damen;L. Liu;G. Krystal;K. Coggeshall
通讯作者：
George Chacko;S. Tridandapani;J. Damen;L. Liu;G. Krystal;K. Coggeshall