Fields T A, Casey P J
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC 27710-3686, USA.
Biochem J. 1997 Feb 1;321 ( Pt 3)(Pt 3):561-71. doi: 10.1042/bj3210561.
Pertussis toxin (PTX) has been widely used as a reagent to characterize the involvement of heterotrimeric G-proteins in signalling. This toxin catalyses the ADP-ribosylation of specific G-protein alpha subunits of the Gi family, and this modification prevents the occurrence of the receptor-G-protein interaction. This review focuses on the biochemical properties and signalling of those G-proteins historically classified as 'PTX-resistant' due to the inability of the toxin to influence signalling through them. These G-proteins include members of the Gq and G12 families and one Gi family member, i.e. Gz. Signalling pathways controlled by these G-proteins are well characterized only for Gq family members, which activate specific isoforms of phospholipase C, resulting in increases in intracellular calcium and activation of protein kinase C (PKC), among other responses. While members of the G12 family have been implicated in processes that regulate cell growth, and Gz has been shown to inhibit adenylate cyclase, the specific downstream targets to these G-proteins in vivo have not been clearly established. Since two of these proteins, G12 alpha and Gz alpha, are excellent substrates for PKC, there is the potential for cross-talk between their signalling and Gq-dependent processes leading to activation of PKC. In tissues that express these G-proteins, a number of guanine-nucleotide-dependent, PTX-resistant, signalling pathways have been defined for which the G-protein involved has not been identified. This review summarizes these pathways and discusses the evidence both for the participation of specific PTX-resistant G-proteins in them and for the regulation of these processes by PKC.
百日咳毒素（PTX）已被广泛用作一种试剂，以表征异源三聚体G蛋白在信号传导中的作用。这种毒素催化Gi家族特定G蛋白α亚基的ADP核糖基化，这种修饰会阻止受体 - G蛋白相互作用的发生。本综述重点关注那些由于毒素无法通过它们影响信号传导而在历史上被归类为“对PTX耐药”的G蛋白的生化特性和信号传导。这些G蛋白包括Gq和G12家族的成员以及一个Gi家族成员，即Gz。仅对于Gq家族成员，由这些G蛋白控制的信号通路已得到充分表征，它们激活磷脂酶C的特定同工型，导致细胞内钙增加和蛋白激酶C（PKC）激活等反应。虽然G12家族成员已被认为参与调节细胞生长的过程，并且Gz已被证明可抑制腺苷酸环化酶，但这些G蛋白在体内的特定下游靶点尚未明确确定。由于其中两种蛋白，G12α和Gzα，是PKC的优良底物，它们的信号传导与Gq依赖性过程之间存在相互作用导致PKC激活的可能性。在表达这些G蛋白的组织中，已经定义了许多鸟嘌呤核苷酸依赖性、对PTX耐药的信号通路，其中涉及的G蛋白尚未确定。本综述总结了这些通路，并讨论了特定的对PTX耐药的G蛋白参与其中以及PKC对这些过程进行调节的证据。
