原标题：细胞信号通路详解之G蛋白偶联受体（GPCR）信号通路

G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The G proteins that associate with GPCRs are heterotrimeric, meaning they have three different subunits: an alpha subunit, a beta (β) subunit, and a gamma (γ) subunit. Two of these subunits - alpha (α-) and gamma (γ) - are attached to the plasma membrane by lipid anchors (Figure 1). Ligand binding to the GPCR causes a change in the receptor conformation that in turn binds and activates the G-protein. The active form of the G-protein is then released from the surface of the receptor, dissociating into its α- and β/γ subunits. Both subunits will then activate their specific effectors, causing the release of second messengers. These messengers are recognised by protein kinases leading to their activation and triggering the signaling cascade towards a cellular event.

第二信使释放酶主要分为两类，均被不同类型的G蛋白激活或灭活（图2和3）。Gαs和Gαi亚型分别激活或灭活腺苷酸环化酶，该酶将三磷酸腺苷（ATP）转换成环状单磷酸腺苷（cAMP），在此过程中释放出无机焦磷酸盐。其他亚型（例如Gαq或Gαo）将激活磷酸肌醇磷脂酶C酶（PLC），该酶将磷脂酰肌醇4,5-双磷酸酯（PIP2）水解为sn-1,2，二酰基甘油（DAG）和肌醇1,4， 5-三磷酸（IP3）。IP3与内质网钙通道结合，触发钙离子释放到细胞质中。

There are two main groups of second messenger releasing enzymes and both are activated or inactivated by different types of G-proteins (Figure 2 & 3). Subtypes Gαs and Gαi either activate or inactivate, respectively, the adenylate cyclase enzyme which converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP), releasing inorganic pyrophosphate in the process. Other subtypes such as Gαq or Gαo will alternatively activate the phospho-inositol phospholipase C enzyme (PLC), which hydrolyses phosphatidylinositol-4,5- biphosphate (PIP2) into sn-1,2 diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). The IP3 binds to an endoplasmic reticulum calcium channel, triggering the release of calcium ions into the cytosol.

GPCR功能与细胞对外部因素的感测有关，这些外部因素包括加味剂，味觉配体，光，金属，神经递质，生物胺，脂肪酸，氨基酸，肽，蛋白质，类固醇和其他脂质。与大量受体相关的配体的大量可能性已导致GPCR与大量生理和病理状况的关联。这些包括疼痛，哮喘，癌症，心血管疾病，胃肠道疾病，中枢神经系统疾病等。

GPCR function is associated with cell sensing of external factors including odorants, taste ligands, light, metals, neurotransmitters, biogenic amines, fatty acids, amino acids, peptides, proteins, steroids and other lipids. The large number of possibilities of ligands associated with the huge quantity of receptors has led to the association of GPCRs with a large number of physiological and pathological conditions. These include pain, asthma, cancer, cardiovascular diseases, gastrointestinal diseases, CNS diseases and others.

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