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有丝分裂原活化蛋白激酶激酶激酶3(MEKK3)是MAP3K超家族MEKK/STE11亚群中的一种丝氨酸/苏氨酸蛋白激酶。在一定条件下MEKK3能够活化多种下游MAPK,包括细胞外信号调节激酶(ERK)~(1/2)、c-Jun氨基末端激酶(JNK)、p38以及ERK5。MEKK3组成性地表达于固有免疫细胞和适应性免疫细胞,在免疫应答过程中以及免疫细胞发育、分化、活化和存活过程中起着重要的调节作用。MEKK3不仅参与调节促炎症细胞因子和Toll样受体(TLR)诱导的IKK/NF-κB活化以及多种下游MAPK活化,还参与调节T细胞稳态、活化和分化过程。本文综述了MEKK3蛋白结构、磷酸化与活化机制,及其在炎症和免疫应答中参与调节的信号通路,特别是对促炎因子和TLR引起的固有免疫应答和T细胞表面受体(TCR)介导的适应性免疫应答中信号通路的调节作用。
Mitogen-activated protein kinase kinase kinase 3 (MEKK3) is a serine / threonine protein kinase in the MAPK superfamily MEKK / STE11 subpopulation. Under certain conditions, MEKK3 activates a variety of downstream MAPKs, including extracellular signal-regulated kinase (ERK) ~ (1/2), c-Jun N-terminal kinase (JNK), p38, and ERK5. MEKK3 is constitutively expressed in innate immune cells and adaptive immune cells and plays an important regulatory role in the immune response and in the process of immune cell development, differentiation, activation and survival. MEKK3 not only participates in the regulation of IKK / NF-κB activation induced by proinflammatory cytokines and Toll-like receptors (TLRs), but also many downstream MAPKs. It is also involved in the regulation of T cell homeostasis, activation and differentiation. This review summarizes the protein structure, phosphorylation and activation mechanisms of MEKK3, and its signaling pathways involved in the regulation of inflammation and immune responses, in particular, the innate immune responses induced by proinflammatory cytokines and TLRs, and the T cell surface receptor (TCR) Regulation of signaling pathways in adaptive immune responses.