Signal transduction second messenger cascades

Second messenger cascades in vomeronasal sensory cells Although the functional implications of the PLC/IP3 cascade in olfactory neurons of nasal epithelium remains mysterious, there is mounting evidence that phospholipase C is a key enzyme for signal transduction in chemosensory neurons... 

More recent research has focused on examining underlying commonalities in the biochemical actions of the mood stabilizers used to treat bipolar disorder (Zhou et al., 2005), in studies of postmortem brain tissue (Post et al., 2003), and in signal transduction pathways and regulation of gene expression (Bezchlibnyk and Young, 2002). For example, altered levels or function of G-protein alpha subunits and protein kinase A and C have been found in bipolar patients, as well as disruption in second messenger cascades such as the ERK/MAPK pathways. 

Lin A, Smeal T, Binetruy B, et al Control of AP-1 activity by signal transduction cascades. Adv Second Messenger Phosphoprotein Res 28 255-260, 1993 lindefors N, Linden A, Brene S, et al CCK peptides and mRNA in the human brain. Prog Neurobiol 40 671-690, 1993... 

Phospholipase C (PTC, EC 3.1.4.3) catalyzes the hydrolysis of the phosphodiester bond in phospholipids. It releases the second messenger molecule diacylglycerin (DAG) important in the signal transduction cascade and a phosphorylated headgroup . The active site of the enzyme contains three Zn ions with two of them in close proximity. Only few crystal structures are solved until now " . ... 

Another class of receptors mediate intracellular responses through Ca2+ mobilisation. A specific class of phospholipids, the phosophoinositides play an important role in signal transduction from receptors at the plasma membrane. The cellular responses that use phosphoinositide hydrolysis and Ca2+ mobilisation are diverse, they include general metabolism, secretion, contraction, phototransduction and proliferation. An imbalance of the second messenger system in the proliferation cascade may be responsible for normal cells becoming cancerous. 

Bioactive peptides usually occur in small quantities and concentrations within complex biological matrices. This is for two reasons firstly, bioactive peptides interact with a cell-surface-bound receptor to convey a message to the cell that is further amplified by second messengers or other signal transduction cascades. Therefore, they are usually produced in low concentrations along with other peptides. Secondly, because the bioactive peptides usually affect carefully balanced biological regulatory systems, their localization and half-life are precisely controlled... 

It is commonly agreed that the signal transduction cascade, which is much less understood, is also of tremendous importance in mediating the effect of psychotropics. Components of this cascade include G proteins, ion channels, second messengers, and protein kinases (Manji et al. 1995). Interindividual and crossethnic variations in the genes coding these proteins likely exist and may also be responsible for the individual variability in drug response observed clinically. 

Figure 28-2 Signal transduction by cell-surface receptors that are coupled to G-proteins.Two seven-transmembrane domains, coupled to different G-proteins (Gs, and G,) are shown. Activation of Gs leads to stimulation of the effector enzyme adenylate cyclase and the production of a cAMP second messenger, causing the activation of protein kinase A (PKA) and the initiation of potential phosphorylation cascades. Activation of G leads to stimulation of the effector enzyme phospholipase C p and the production of IP3 and diacylglycerol (DAG) second messengers, one effect of which is to activate protein kinase C (PKC) and Initiate a potential phosphorylation cascade. (From Conn PM.Mefmed S, eds.Textbook of endocrinolog/.Towanta Nj Humana Press 1997.)...

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