Gudermann T
Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Germany.
Novartis Found Symp. 2001;239:68-79; discussion 80-4, 150-9. doi: 10.1002/0470846674.ch7.
It has only recently been fully realized that G protein-coupled receptors and G proteins play crucial roles in the regulation of cell growth, differentiation and even tumour formation. Naturally occurring mutations in G protein-coupled receptors and in G protein alpha subunits result in uncontrolled cellular proliferation resulting in distinct human diseases. One important mechanism to transduce mitogenic signals from the cell membrane to the cell nucleus is the engagement of the extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) cascade. A multitude of distinct signal transduction pathways have been deciphered which connect G proteins with the ERK cascade. Both receptor and non-receptor tyrosine kinases play pivotal roles in these signalling pathways. Mitogenic signalling by G protein-coupled receptors can be regarded as a complex interplay between signals emanating from different classes of cell surface receptors which ultimately converge upon a small subset of central signalling proteins in the cell. The characterization of receptor-, G protein- and tyrosine kinase-specific contributions to mitogenic signalling in a particular cell and the identification of proteins serving as a point of convergence in the mitogenic signalling cascade may ultimately allow the design of novel pharmacological approaches to treat diseases involving unrestricted cell proliferation.
直到最近人们才充分认识到，G蛋白偶联受体和G蛋白在细胞生长、分化乃至肿瘤形成的调控中发挥着关键作用。G蛋白偶联受体和G蛋白α亚基的天然突变会导致细胞增殖失控，进而引发各种人类疾病。将有丝分裂原信号从细胞膜传导至细胞核的一个重要机制是细胞外信号调节激酶（ERK）-丝裂原活化蛋白激酶（MAPK）级联反应的激活。现已破译了许多不同的信号转导途径，这些途径将G蛋白与ERK级联反应联系起来。受体酪氨酸激酶和非受体酪氨酸激酶在这些信号通路中都起着关键作用。G蛋白偶联受体介导的有丝分裂信号可被视为源自不同类别的细胞表面受体的信号之间的复杂相互作用，这些信号最终汇聚于细胞内一小部分核心信号蛋白上。明确特定细胞中受体、G蛋白和酪氨酸激酶对有丝分裂信号的特异性贡献，以及鉴定作为有丝分裂信号级联反应汇聚点的蛋白质，最终可能有助于设计新的药理学方法来治疗涉及不受控制的细胞增殖的疾病。
