Jensen J
Department of Physiology, National Institute of Occupational Health, Oslo, Norway.
Br J Pharmacol. 2007 Jun;151(4):423-5. doi: 10.1038/sj.bjp.0707248. Epub 2007 Apr 23.
The proteome characterising a specific cell type makes up a unique intracellular signalling network and signalling has to be studied in a cell specific manner. Beta-adrenergic receptors are coupled to production of cAMP and PKA was initially believed to be the only protein activated by cAMP. However, cAMP-mediated signalling via Epac and Rap1 has emerged as an important contributor to cAMP signalling. In the current issue of the British Journal of Pharmacology, Kanda and Watanabe report that adrenaline stimulates glucose uptake in vascular smooth muscle cells. With pharmacological methods, supplemented with small interfering RNA against Rap1, the authors demonstrate that adrenaline increases glucose uptake via G(s), adenylate cyclase, cAMP and Rap1 activation. The authors could document neither PKA nor Epac as the receptor for cAMP mediating the effect. Although there is no doubt that Rap1 mediates adrenaline-stimulated glucose uptake in vascular smooth muscle cells, it may be too early to exclude PKA and Epac.
表征特定细胞类型的蛋白质组构成了一个独特的细胞内信号网络，并且必须以细胞特异性的方式来研究信号传导。β-肾上腺素能受体与cAMP的产生相关联，并且蛋白激酶A（PKA）最初被认为是唯一被cAMP激活的蛋白质。然而，经由交换蛋白直接激活cAMP（Epac）和Rap1的cAMP介导的信号传导已成为cAMP信号传导的一个重要因素。在本期《英国药理学杂志》中，神田和渡边报道肾上腺素可刺激血管平滑肌细胞摄取葡萄糖。通过药理学方法，并辅以针对Rap1的小干扰RNA，作者证明肾上腺素通过G(s)、腺苷酸环化酶、cAMP和Rap1激活来增加葡萄糖摄取。作者既未证明PKA也未证明Epac是介导该效应的cAMP受体。尽管毫无疑问Rap1介导血管平滑肌细胞中肾上腺素刺激的葡萄糖摄取，但排除PKA和Epac可能还为时过早。
