研究生细胞信号转导下.pptVIP

表10-1 细胞外信息物质影响细胞功能的途径 离子通道型受体/配体门控离子通道(ion channel linked receptors) 受体本身由配体结合位点与离子通道两部分构成。 受体与配体结合后即有酪氨酸蛋白激酶活性，既可导致受体自身磷酸化，也可催化底物蛋白的特定酪氨酸残基磷酸化 In a reaction catalyzed by the enzyme adenylyl cyclase, cyclic AMP (cAMP) is synthesized from ATP through a cyclization reaction that removes two phosphate groups as pyrophosphate (—); a pyrophosphatase drives this synthesis by hydrolyzing the released pyrophosphate to phosphate . Cyclic AMP is unstable in the cell, because it is itself hydrolyzed by a specific phosphodiesterase to form 5’-AMP, as indicated This nerve cell in culture is responding to the neurotransmitter serotonin, which acts through a G-protein-linked receptor to cause a rapid rise in the intracellular concentration of cyclic AMP. To monitor the cyclic AMP level, the cell has been loaded with a fluorescent protein that changes its fluorescence when it binds cyclic AMP. Blue indicates a low level of cyclic AMP, yellow an intermediate level, and red a high level. The binding of cAMP to the regulatory subunits induces a conformational change, causing these subunits to dissociate from the catalytic subunits, thereby activating the kinase activity of the catalytic subunits. The release of the catalytic subunits requires the binding of more than two cAMP molecules to the regulatory subunits in the tetramer. This requirement greatly sharpens the response of the kinase to changes in cyclic AMP concentration. Mammalian cells have at least two types of PKAs: type I is mainly in the cytosol, whereas type II is bound via its regulatory subunit and special anchoring proteins to the plasma membrane, nuclear membrane, mitochondrial outer membrane, and microtubules. In all cases, however, once the catalytic subunits are freed and active, they can migrate into the nucleus (where they can phosphorylate gene regulatory proteins), while the regulatory subunits remain in the cytoplasm. The binding of an extracellular signal molecule to its G-protein-linked receptor l