細胞膜受容体を介したシグナルトランスダクションの解析
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The elucidation for the mechanism of receptor-mediated signal transduction has been the aim of our extensive studies. Cyclic AMP, which was controled by membrane adenylyl cyclase, was an intracellular signal (the first second messenger in cells proposed by Sutherland) given by hormones and neurotransmitters. The GTP-binding (G) proteins play an important role in communication between membrane receptors and the adenylyl cyclase catalytic unit. One (Gs) of the G proteins is involved in the activation, while the other (Gi) is involved in the inhibition of adenylyl cylase. Islet-activating protein (IAP, pertussis toxin, PTX) catalyses the transfer of the ADP-ribose moiety of NAD to the a subunit of Gi, resulting in a complete loss of the Gi functions. In some cases, arachidonic acid (AA) regulates cell functions as a second messenger. AA serves as a precursor to a number of biologically active lipids including prostaglandins and leukotrienes. Activation of cell surface receptors of many cell types results in the release of AA from membrane phospholipids by phospholipase A_2 (PLA_2). A new family of PLA_2 has been discovered in the cytosol of various cells. The activation of receptor-mediated AA release by cytosolic PLA_2 was also regulated by PTX-sensitive G proteins. PTX treatment inhibited cell growth of fibroblasts by serum and growth factors. G proteins have been involved in receptor-receptor interactions in neuronal cells. These findings suggest the regulatory roles of cell surface receptors-coupled G proteins in signal transductions and cell functions.
- 公益社団法人日本薬学会の論文
- 1996-04-25
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- 細胞膜受容体を介したシグナルトランスダクションの解析