INTERACTION OF IL-2R-BETA AND GAMMA(C) CHAINS WITH JAK1 AND JAK3 - IMPLICATIONS FOR XSCID AND XCID
INTERACTION OF IL-2R-BETA AND GAMMA(C) CHAINS WITH JAK1 AND JAK3 - IMPLICATIONS FOR XSCID AND XCID
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DOI：
10.1126/science.7973658
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发表时间：
1994-11-11
期刊：
影响因子：
56.9
通讯作者：
LEONARD, WJ
中科院分区：
文献类型：
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作者：
RUSSELL, SM;JOHNSTON, JA;LEONARD, WJ
白介素2(IL-2)信号需要白介素2受体β(IL-2Rβ)和常见的伽马(γ(C))链的二聚化。Gamma(C)基因突变可导致X连锁严重联合免疫缺陷(XSCID)。IL-2、IL-4、IL-7(已知其受体含有γ(C))和IL-9(其受体含有γ(C))诱导Janus家族酪氨酸激酶JAK1和JAK3的酪氨酸磷酸化和激活。JAK1和JAK3分别与IL-2Rβ和Gamma(C)相关；IL-2诱导JAK3-IL-2Rβ和增加JAK3-Gamma(C)的相关性。伽马(C)和一个伽马(C)点突变的截断导致中度X连锁联合免疫缺陷(XCID)，降低了伽马(C)与JAK3的关联性。因此，至少在一些XSCID和XCID患者中，Gamma(C)突变阻止了正常的JAK3激活，这表明JAK3的突变可能导致XSCID样表型。
Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta (IL-2R beta) and common gamma (gamma(c)) chains. Mutations of gamma(c) can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma(c)) and IL-9 (whose receptor is shown here to contain gamma(c)) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma(c), respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma(c) associations. Truncations of gamma(c), and a gamma(c), point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma(c)-Jak3 association. Thus, gamma(c) mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.