CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex
CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex
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DOI：
10.1016/j.immuni.2006.08.020
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发表时间：
2006-10-01
期刊：
影响因子：
32.4
通讯作者：
Bucala, Richard
中科院分区：
文献类型：
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作者：
Shi, Xuerong;Leng, Lin;Bucala, Richard
巨噬细胞移动抑制因子（MIF）受体（CD 74）最近被克隆，但其信号转导机制尚不清楚。我们假设信号传导需要额外的分子，如CD 44，它激活非受体酪氨酸激酶。我们利用CD 74和CD 44缺陷型CCS-7/M6细胞来产生表达CD 74、CD 44和缺乏胞浆内信号传导结构域的截短的CD 44的稳定转染子。CD 74单独介导MIF结合，然而，MIF诱导的ERK 1和ERK 2激酶磷酸化需要全长CD 44的共表达。MIF结合与CD 74和CD 44的丝氨酸磷酸化有关。使用siRNA或激酶抑制剂的研究表明，MIF诱导的ERK 1和ERK 2通过CD 44激活需要Src酪氨酸激酶。对CD 74、CD 44和CD 74-CD 44转化体和相应突变体细胞的研究表明，CD 74和CD 44是MIF保护细胞免于凋亡所必需的。这些数据确立了CD 44作为导致MIF信号转导的CD 74受体复合物的组成成员。
The macrophage migration inhibitory factor (MIF) receptor (CD74) was cloned recently, but the signaling mechanism is not evident. We hypothesized that signaling requires an additional molecule such as CD44, which activates nonreceptor tyrosine kinases. We utilized the CD74- and CD44-deficient CCS-7/M6 cell to create stable transfectants expressing CD74, CD44, and a truncated CD44 lacking its intracytoplasmic signaling domain. CD74 alone mediated MIF binding; however, MIF-induced ERK1 and ERK2 kinase phosphorylation required the coexpression of full-length CD44. MIF binding was associated with the serine phosphorylation of CD74 and CD44. Investigations that used siRNA or kinase inhibitors indicate that MIF-induced ERK1 and ERK2 activation through CD44 required the Src tyrosine kinase. Studies of CD74, CD44, and CD74-CD44 transformants and corresponding mutant cells showed that CD74 and CD44 were necessary for MIF protection from apoptosis. These data establish CD44 as an integral member of the CD74 receptor complex leading to MIF signal transduction.