Rozengurt E
Department of Medicine, School of Medicine and Molecular Biology Institute, University of California, Los Angeles 90095-1786, USA.
J Cell Physiol. 1998 Dec;177(4):507-17. doi: 10.1002/(SICI)1097-4652(199812)177:4<507::AID-JCP2>3.0.CO;2-K.
Neuropeptides, including mammalian bombesin-like peptides, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. These signaling peptides exert their characteristic effects on cellular processes by binding to specific G protein-coupled receptors (GPCR) on the surface of their target cells. Typically, the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho. The purpose of this article is to review recent advances in unraveling the pathways that play a role in transducing mitogenic and migratory responses induced by G protein-coupled neuropeptide receptor agonists.
神经肽，包括哺乳动物中的蛙皮素样肽，作为强大的细胞生长因子，参与了包括发育、炎症和恶性转化在内的各种正常和异常过程。这些信号肽通过与其靶细胞表面特定的G蛋白偶联受体（GPCR）结合，对细胞过程发挥其特征性作用。通常，神经肽与其同源GPCR的结合会触发多个信号转导途径的激活，这些途径以协同和组合的方式将促有丝分裂信号传递到细胞核并促进细胞增殖。脂质衍生的第二信使合成迅速增加，随后蛋白磷酸化级联反应被激活，这是对神经肽的重要早期反应。信号转导中一个新出现的主题是，这些激动剂还能诱导细胞蛋白包括非受体酪氨酸激酶p125fak以及衔接蛋白p130cas和桩蛋白的快速协同酪氨酸磷酸化。这种酪氨酸磷酸化途径依赖于肌动蛋白细胞骨架的完整性，并且需要功能性的Rho。本文的目的是综述在揭示由G蛋白偶联神经肽受体激动剂诱导的促有丝分裂和迁移反应转导过程中发挥作用的途径方面的最新进展。
