Fcγ受体IIb型肌糖和蛋白质磷酸酶信号诱导招聘transductory人类b细胞的复杂。
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Sarmay G, G Koncz, Pecht我Gergely J
Fcγ受体IIb型肌糖和蛋白质磷酸酶信号诱导招聘transductory人类b细胞的复杂。
Immunol。1997年6月1;57 (1 - 3):159 - 64。
- PubMed ID
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9232445 (在PubMed]
- 文摘
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Co-clustering Fc伽马RIIb和b细胞受体(BCR)通过阻断BCR刺激信号转导抑制细胞的激活。的immunoreceptor tyrosine-based抑制主题(ITIM) Fc伽马RIIb变得酪氨酰磷酸化(P-ITIM)在与BCR co-clustering然后P-ITIM与一些信号分子,其中一些消极的调节细胞的激活过程。分子被人类Fc的P-ITIM伽马RIIb尚未为特征的。为了亲和分离人类Fc的潜在功能的伴侣分子γRIIb,合成肽设计覆盖几乎整个细胞内Fc伽马RIIb领域,包括Fc伽马RIIb2特定序列包含磷酸化的延伸和non-phosphorylated ITIM。我们报告在这里,几个酪氨酰磷酸化蛋白质绑定到P-ITIM肽休息和激活b细胞溶解产物,在53-56 kDa是最突出的一个。的一小部分53-56 kDa乐队被确定为蛋白质酪氨酸激酶(PTK),林恩也必将ITIM肽,指向其启动Fc伽马RIIb-mediated负调控作用。P-ITIM中酪氨酸磷酸化组件相关联,145 kDa一被认定为肌醇多磷酸盐5-phosphatase,船和72 kDa蛋白质作为蛋白质酪氨酸磷酸酶(PTP) SHP2而SHP1没有检测到。磷酸酶活性测定表明,P-ITIM绑定大约五倍比ITIM船和高四倍PTP活动包含肽。此外,我们发现PKC和MAPK ITIM和P-ITIM肽沉淀样本。自人类b细胞表达Fc伽马RIIb1和FcγRIIb2,在19个氨基酸插入不同细胞质尾前,我们调查了组件绑定到Fc伽马RIIb1和Fc伽马RIIb2特定序列。 Synthetic peptide representing Fc gamma RIIb1 and Fc gamma RIIb2 specific sequences weakly bound unidentified tyr phosphorylated proteins at 50-56 kDa, while the insert itself did not bind a detectable amount of protein. Neither of the ITIM or P-ITIM bound molecules were observed in samples precipitated with peptides corresponding to Fc gamma RIIb1 or Fc gamma RIIb2 specific sequences. These observations suggest that protein kinases associate with both ITIM and P-ITIM of human Fc gamma RIIb, Lyn being responsible for the tyrosyl phosphorylation of ITIM. SHIP and SHP2 phosphatases selectively bind to the phosphorylated ITIM. Based on these data we assume that SHIP and SHP2 recruited in vivo to the Fc gamma RIIb co-clustered BCR are responsible for the Fc gamma RIIb mediated negative regulation of human B-cell activation.