![]() ![]() In the center, binding of ligands to a GPCR (receptor) activates phospholipase C (PLC the effector), to generate two second messengers, DAG and IP 3, which activate protein kinase C (PKC the target) and release calcium from intracellular stores, respectively. On the left, binding of growth factors to a receptor tyrosine kinase (RTK the receptor) can activate PI3K (the effector) to generate PIP 3 (the second messenger), which activates Akt (the target). On the right, binding of agonists to a GPCR (the receptor) can activate adenylyl cyclase (the effector) to produce cAMP (the second messenger) to activate protein kinase A (PKA the target). Indicated are three examples of a receptor activating an effector to produce a second messenger that modulates the activity of a target. Second messengers disseminate information received from cell-surface receptors. The activation of multiple effector pathways by a single plasma membrane receptor and the production of multiple second messengers by each effector can generate a high degree of amplification in signal transduction, and stimulate diverse, pleiotropic, responses depending on the cell type. Three classic second messenger pathways are illustrated in Figure 1: (1) activation of adenylyl cyclase by G-protein-coupled receptors (GPCRs) to generate the cyclic nucleotide second messenger 3′-5′-cyclic adenosine monophosphate (cAMP) (2) stimulation of phosphoinositide 3-kinase (PI3K) by growth factor receptors to generate the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP 3) and (3) activation of phospholipase C by GPCRs to generate the two second messengers membrane-bound messenger diacylglycerol (DAG) and soluble messenger inositol 1,4,5-trisphosphate (IP 3), which binds to receptors on subcellular organelles to release calcium into the cytosol. The second messenger then diffuses rapidly to protein targets elsewhere within the cell, altering the activities as a response to the new information received by the receptor. 2014) ligand binding alters the protein conformation of the receptor such that it stimulates nearby effector proteins that catalyze the production or, in the case of ions, release or influx of the second messenger. ![]() ![]() These second messengers broadcast the initial signal (the “first message”) that occurs when a ligand binds to a specific cellular receptor (see Heldin et al. Signals received by receptors at the cell surface or, in some cases, within the cell are often relayed throughout the cell via generation of small, rapidly diffusing molecules referred to as second messengers. ![]()
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