Taskén K, Skålhegg B S, Taskén K A, Solberg R, Knutsen H K, Levy F O, Sandberg M, Orstavik S, Larsen T, Johansen A K, Vang T, Schrader H P, Reinton N T, Torgersen K M, Hansson V, Jahnsen T
Institute of Medical Biochemistry, University of Oslo, Norway.
Adv Second Messenger Phosphoprotein Res. 1997;31:191-204. doi: 10.1016/s1040-7952(97)80019-5.
A large number of hormones, neurotransmitters, and other signaling substances that bind to G-protein-coupled cell-surface receptors have their signals converge at one sole second messenger, cAMP. The question of how specificity can be maintained in a signal-transduction system in which many extracellular signals leading to a vast array of intracellular responses are all mediated through one second-messenger system has been the subject of thorough investigation and a great deal of speculation. An increasing number of cAK isozymes, consisting of homo- or heterodimers of R subunits (RIalpha, RIbeta, RIIalpha, RIIbeta) with associated catalytic subunits (C alpha, Cbeta, Cgamma), may, at least in part, explain this specificity. The various cAK isozymes display distinct biochemical properties, and the heterogeneous subunits of cAK reveal cell-specific expression and differential regulation at the level of gene transcription, mRNA stability, and protein stability in response to a wide range of hormones and other signaling substances. The existence of a number of anchoring proteins specific to either RIIalpha or RIIbeta, and which localize cAKII isozymes toward distinct substrates at defined subcellular loci, strongly supports the idea that specific functions can be assigned to the various cAK isozymes. The demonstration that selective activation of cAKI is necessary and sufficient for cAMP-mediated inhibition of T-cell proliferation, and the observation that T-cell activation is associated with redistribution and colocalization of cAKI to the TCR, is also compatible with the notion of isozyme-specific effects.
大量与G蛋白偶联细胞表面受体结合的激素、神经递质及其他信号物质，其信号都汇聚于一种单一的第二信使——环磷酸腺苷（cAMP）。在一个信号转导系统中，众多细胞外信号引发大量细胞内反应，却都通过一个第二信使系统介导，那么如何维持信号特异性这一问题，一直是深入研究和大量推测的主题。越来越多的cAK同工酶，由R亚基（RIα、RIβ、RIIα、RIIβ）的同型或异型二聚体与相关催化亚基（Cα、Cβ、Cγ）组成，这或许至少能部分解释这种特异性。各种cAK同工酶展现出不同的生化特性，cAK的异质亚基在基因转录、mRNA稳定性和蛋白质稳定性层面，针对多种激素及其他信号物质，呈现出细胞特异性表达和差异调节。存在一些分别特异于RIIα或RIIβ的锚定蛋白，它们将cAKII同工酶定位于特定亚细胞位点的不同底物上，这有力地支持了可赋予各种cAK同工酶特定功能这一观点。cAMP介导的T细胞增殖抑制需要cAKI的选择性激活且这一激活是充分的，以及观察到T细胞激活与cAKI向TCR的重新分布和共定位相关，这也与同工酶特异性效应的概念相符。
