Human CD4/CD45RA+ and CD4/CD45RA- T cell subsets express CD4-p56lck complexes, CD4-associated lipid kinases, TCR/CD3-p59fyn complexes, and share similar tyrosine kinase substrates.
Human CD4/CD45RA+ and CD4/CD45RA- T cell subsets express CD4-p56lck complexes, CD4-associated lipid kinases, TCR/CD3-p59fyn complexes, and share similar tyrosine kinase substrates.
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人CD4/CD45RA和CD4/CD45RA-T细胞亚群表达CD4-p56lck复合物、CD4相关脂质激酶、TCR/CD3-p59fyn复合物，并且具有相似的酪氨酸激酶底物。
DOI：
10.1093/intimm/5.4.409
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发表时间：
1993
影响因子：
4.4
通讯作者：
Rudd,CE
中科院分区：
文献类型：
--
作者：
Rothstein,DM;daSilva,A;Sugita,K;Yamamoto,M;Prasad,KV;Morimoto,C;Schlossman,SF;Rudd,CE
T细胞的激活似乎受蛋白酪氨酸激酶(PTKs)和蛋白酪氨酸磷酸酶(PTPase)之间的相互作用调节。P56lck和p59fync分别与CD4和TCR-CD3相关。CD45家族的跨膜PTPase已被证明能够在体外调节这些受体相关的PTKs的活性。在MAN中，CD45包含五种不同的亚型，它们的分布定义了具有不同激活要求和体外功能的T细胞亚群。几个小组已经报道了不同亚型的CD45和CD2、CD4以及TCR-CD3复合体之间的物理相互作用。鉴于在表达不同亚型的CD_4~+亚群中CD_(45)和PTK之间的潜在调节相互作用，我们研究了CD_4相关和TCR-CD_3−相关的PTK活性、相关的磷脂酰肌醇(PI)激酶和来自外周血的CD_(45)RA−CD_4+T细胞系中酪氨酸磷酸化的底物。这两个亚群都表达CD4相关的p56lck和TCR-CD3相关的p59fynkinase，它们分别在Y-394和Y-420的自磷酸化位点表现出相同的胞外磷酸化。此外，两个亚群都表现出与CD4-p56lck相关的PI激酶活性。与这些观察结果相一致的是，抗CD3交联剂在这些CD45RA+和CD45RA−+T细胞系中诱导了类似的胞内底物的磷酸化。这些观察表明，尽管CD45亚型与CD4或TCR-CD3之间可能存在相互作用，但仅仅表达CD45RA亚型本身并不能改变受体相关激酶或它们的细胞内靶点的存在。
T cell activation appears to be regulated by an interplay between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). p56lckand p59fynhave been found to associate with CD4 and TCR-CD3 respectively. The CD45 family of transmembrane PTPases has been shown to be able to regulate the activities of these receptor-associated PTKsin vitro. In man, CD45 contains five different isoforms whose distribution defines subsets of T cells having distinct activation requirements andin vitrofunctions. Several groups have reported a physical interaction between distinct isoforms of CD45 and CD2, CD4, and the TCR-CD3 complex. Given the potential regulatory interaction between CD45 and PTKs in CD4+subsets expressing different CD45 isoforms, we have examined CD4 associated and TCR-CD3−associated PTK activities, associated phosphatidyl inositoi (PI) kinases and substrates of tyrosine phosphoryiation in CD45RA+and CD45RA−CD4+T cell lines derived from peripheral blood. Both subsets express CD4-assoclated p56lckand TCR-CD3-associated p59fynkinases which exhibit identicalin vitrophosphoryiation at the Y-394 and Y-420 autophosphorylation sites respectively. Further, both subsets exhibited PI kinases activity associated with CD4-p56lck. Consistent with these observations, anti-CD3 crosslinklng induced the phosphoryiation of a similar spectrum of intracellular substrates in these CD45RA+and CD45RA−CD4+T cell lines. These observations indicate that despite the possible interaction between CD45 isoforms and CD4 or TCR-CD3, the mere expression of the CD45RA isoform does not in and of itself alter the presence of receptorassociated kinases or their intracellular targets.