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1、D103 - Cell Biology - lecture 17 2011 Grant MacGregor cGMP/cAMP - high. Messages are encoded by the change in concentration of the second messenger (riseorfall). Second messengers convey signals by binding to, and altering the conformation and behavior of, selected signaling molecules and effector p
2、roteins. Steady-state concentration of a second messenger is determined by the sum of its rate of synthesis and degradation by specific enzymes (sometimes these are the direct targets of the G-protein). The enzymes (or channels) that modulate intracellular levels of second messengers can switch on a
3、nd off rapidly, leading to change in concentration of a second messenger on a milli-second (ms-1) time scale.,Components of intracellular signal transduction - Second Messengers,D103 - Cell Biology - lecture 17 2011 Grant MacGregor i.e. the half life of cAMP is relatively short. Normal concentration
4、 of cAMP in cytosol is around 10-7M, but this can change by around 20 x within seconds of receipt of a signal (e.g. example at top).,e.g. production of cAMP in response to serotonin (ligand) in neurons. Live neurons are visualized by fluorescence microscopy. A fluorescent dye changes color in respon
5、se to a change in local concentration of cAMP within the cell. Blue = low cAMP; red = highcAMP. Notice howrapidly (20 sec) the change in cAMP occurs following exposure of the cell to serotonin (binds to a GPCR).,D103 - Cell Biology - lecture 17 2011 Grant MacGregor CREB - protein that binds to CRE s
6、equences.,D103 - Cell Biology - lecture 17 2011 Grant MacGregor one hydrophilic, one hydrophobic.,D103 - Cell Biology - lecture 17 2011 Grant MacGregor -D = phosphatidic acid; -A2 = arachidonic acid). Arachidonic acid is important intermediate in synthesis of prostaglandins that play important roles
7、 in inflammation.,D103 - Cell Biology - lecture 17 2011 Grant MacGregor e.g. Ca2+- low; cGMP/cAMP, IP3 - high. cAMP and cGMP are formed and degraded by similar enzymes and share similar targets (i.e. ion channels, protein kinases) suggesting a common evolutionary origin. Phospholipases, lipid kinasesand lipid phosphatasesgenerate lipid second messengers. Vertebrates have multiple PI-PLCs, which enables tissue-specific coupling of variousreceptors to production of IP3 and DAG. Vertebrates have multiple PKCs, which enables a selective response to various lipid second messengers.,
