Second messengers

Second messengers are small, non-protein, in water soluble molecules jsou malé. They are called second, because the first messenger is a signal molecule, which binds to the receptor protein. They are involved in transfering signal in pathways starting by G-protein receptors as well as in pathways starting by enzyme-linked receptors. They are made from easily accesible substrates and have a short half life. Second messengers include cAMP, kalcium cations, cGMP, inositol-1,4,5-trisphospate, diacylglycerol, fosfatidylinositol-3,4,5-trisphosphate and more. Except for calcium cations, second messengers are synthesised by specific enzymes after stimulation of membrane receptors. Afterwards seccond messengers activate proteinkinases, which phosphorylate aminoacids serine or threonine in various intracellular proteins. Phosphorylation changes activity of these proteins in means of activation or inhibition. Activity of second messengers is limited and they are degradated by different enzymes.

thumb | right | 170 px | cAMP

Cyclic adenosinmonophosphate (cAMP)
Cyclic AMP is made from ATP by enzyme adenylate cyclase, which is binded to the cytoplasmatic membrane and activated through G-protein, after binding of signal molecule to it's membrane receptor. cAMP then transfers the signal from cytoplasmatic membrane to the metabolic pathways in cytoplasm. Transfer molecule following the cAMP is usually proteinkinase A (cAMP-dependent proteinkinase), which phosphorylates other proteins. PKA-regulated proteins are involved for example in regulation of glycid and lipid metabolism, transport of water and ions in kideys and more. cAMP doesn't stay in cell for long and is soo transformed by fosfodiesterase to AMP (adenosinmonophosphate).

thumb | right | 170 px | cGMP

Cyclic guanosinmonophosphate (cGMP)
Is formed similiarly to cAMP, meaning it's formed by enzyme guanylate cyclase from GTP. Guanylate cyclase ctivity is activated for ex. by atrial natriuretic peptid (ANP). cGMP activated proteinkinase G (cGMP-dependent proteinkinase), which phosphorylates target proteins. Signál transduction including cGMP use for example rods in eye retina or smooth muscle cells in cavernous bodies of penis.

Second messengers derived from phosphatidylinositol-4,5-bisphosfate
thumb | right | 350 px | Fosfatidylinositolová dráha Phosphatidylinositol-4,5-bisphosfate (PIP2, also PtdIns(4,5)P2) is a phospholipid found in cytoplasmatic membrane. From phosphatidylinositol-4,5-bisfosfate can be synthesised second messengers, which can affect two different proteinkinases.

Phosphatidylinositol-3,4,5-trisphoshate
Phosphatidylinositol-3,4,5-trisphosphate (PIP3, aslo PtdIns(3,4,5)P3) is synthesised by phosphorylation of PIP2 by enzyme phosfatidylinositol-3-kinase (PI3K). It stays binded in inner layer of cytoplasmatic membrane and here activates phosphatidylinositol-dependent kinase 1 (PDK1), which phosphorylates (and by that activatates) proteinkinase B. Proteinkinase B (PKB, also called AKT) phosphorylates proteins that regulate proliferation, buněčný cyklus and apoptózu.

Diacylglycerol a inositol-1,4,5-trisphosphate
Signal molecule bind to a receptor, which leads to an activation of enzyme phospholipase C, which splits phosphatidylinositol-4,5-bisfosfát to 1,2-diacylglycerol (DAG) a inositol-1,4,5-trisphosphate (IP3, also Ins(1,4,5)P3). Both are second messengers. IP3 diffuses through cytosol, and binds to a calcium canal in endoplasmatic reticulum and that opens it. Calcium cations are releases from endoplasmatic reticulum and they raise the Ca2+ level in cytosol. DAG stays immersed in cytoplasmatic membrane. DAG and calcium cations together activateí proteinkinase C, which then phosphorylates proteins associated with cytoskeleton and by that affect contraction, migration and secretion in cells.

Calcium cations
Ca2+ is more regular second messenger than cAMP. Raising of Ca2+ concentration causes contraction of muscle cells or secetion of certain substances. Cells always contain certain level of Ca2+, but extracelular level is much higher than intracelular. Intracelular level is raised by opening of calcium channels in endoplasmatic reticulum, which is caused by binding of IP3 onto this channels. Calcium cations could be accounted for as third messegers. Calcium cations activate other proteins directly or with a help of kalmodulin, protein binding Ca2+. Kalmodulin with binded calcium cations activates CaM-kinases, which phosphorylate other proteins.

Související články

 * Buněčná signalizace
 * Hormony
 * G-protein
 * Insulin