Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India; Department of Studies in Zoology, University of Mysore, Manasagangothri, Mysore, India.
Int Rev Cell Mol Biol. 2018;338:79-109. doi: 10.1016/bs.ircmb.2018.02.003. Epub 2018 Apr 5.
GPCRs, the 7-TM receptors, represent a class of cell surface receptors which modulate a variety of physiological responses. The serpentine structure in addition to contributing the diversity of stimuli these receptors can sense also provides flexibility to the extracellular and intracellular regions where other proteins can interact with and can form functionally active multimeric entities. The range in signaling and physiological responses generated by these receptors can be attributed to a large repertoire of the receptor subtypes as well as their differential coupling to various classes of G-protein subunits and other proteins which facilitate multistate activation. A multistate GPCR can engage diverse signaling molecules, thereby modulating not only the canonical cellular responses but also noncanonical responses typically associated with activation of other cascades such as RTK and MAPK/ERK signaling. Given the crucial involvement of MAP kinase/ERK signaling in cell fate determination specially with respect to regulating cell proliferation, cellular apoptosis, and survival, GPCR-mediated cross-activation of MAPK has been explored in various systems and shown to involve functional integration of multiple pathways. This review describes the present knowledge of the different mechanisms of ERK activation downstream of GPCRs and our present understanding of receptor-dependent and -independent MAPK activation cascades.
G 蛋白偶联受体（GPCRs），即 7 次跨膜受体，是一类细胞表面受体，可调节多种生理反应。除了赋予这些受体感知各种刺激的多样性外，其卷曲的结构还为细胞外和细胞内区域提供了灵活性，其他蛋白质可以在这些区域与受体相互作用，并形成具有功能活性的多聚体实体。这些受体产生的信号转导和生理反应的范围归因于大量的受体亚型，以及它们与各种 G 蛋白亚基和其他促进多态激活的蛋白质的差异偶联。多态 GPCR 可以与不同的信号分子结合，从而不仅调节经典的细胞反应，还调节与其他级联（如 RTK 和 MAPK/ERK 信号）激活相关的非经典反应。鉴于 MAP 激酶/ERK 信号在细胞命运决定中特别是在调节细胞增殖、细胞凋亡和存活方面的关键作用，已经在各种系统中探索了 GPCR 介导的 MAPK 的交叉激活，并表明涉及多种途径的功能整合。本综述描述了 GPCR 下游 ERK 激活的不同机制的现有知识，以及我们目前对受体依赖性和非受体依赖性 MAPK 激活级联的理解。
