BIO SCI D103 Lecture Notes - Lecture 18: Phosphatidylinositol 4,5-Bisphosphate, G Protein–Coupled Receptor, Adenylyl Cyclase

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Camp activates cyclic-amp-dependent protein kinase (pka) which phosphorylates specific serines or threonines on select target proteins including intracellular signaling proteins and effector proteins thereby regulating their activity. In inactive state, pka has two catalytic subunits and two regulatory subunits. Binding of camp alters conformation so catalytic subunits dissociate from complex and released to activate/phosphorylate other target proteins. Regulatory subunits (a-kinase) important for localizing kinase inside the cell. Akaps (a-kinase anchoring proteins): bind to both regulatory subunits and cytoskeleton/organelle membrane, thereby tethering the enzyme complex to a particular subcellular compartment: can also bind to other signaling proteins to form a signaling complex. In unstimulated cells, phosphodiesterase keeps local camp concentration low so bound. In stimulated cells, camp rapidly rises overwhelming phosphodiesterase and activates. Pka also phosphorylates an adjacent phosphodiesterase which rapidly lowers camp concentration to prevent prolonged pka response: negative feedback. Gpcr activated by signal molecule which activates gq protein activating phospholipase.

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