Second messenger system 1800732 224330251 2008-07-08T11:06:19Z 76.175.161.191 /* Examples */ In [[cell physiology]], a '''secondary messenger system''' (also known as a '''second messenger system''') is a method of cellular signaling, whereby a diffusable signaling molecule is rapidly generated/released which can then go on to activate effector proteins within the cell to exert a cellular response. Secondary messengers are a component of [[signal transduction]] cascades. Secondary messenger systems can be activated by diverse means, either by activation of enzymes that synthesise them, as is the case with the activation of cyclases which synthesise cyclic nucleotides, or by opening of ion channels to allow influx of metal ions, such as in Ca<sup>2+</sup> signalling. These small molecules may then go on to exert their effect by binding to and activating effector molecules such as protein kinases, ion channels and a variety of other proteins, thus continuing the signalling cascade. ==Types of secondary messenger molecules== There are three basic types of secondary messenger molecules: * '''[[hydrophobe|Hydrophobic]] molecules:''' water-insoluble molecules, like [[diglyceride|diacylglycerol]], [[inositol trisphosphate|IP<sub>3</sub>]], and [[phosphatidylinositol]]s, which are membrane-associated and diffuse from the [[plasma membrane]] into the [[juxtamembrane]] space where they can reach and regulate membrane-associated ''[[effector protein]]s'' * '''[[hydrophile|Hydrophilic]] molecules:''' water-soluble molecules, like [[Cyclic adenosine monophosphate|cAMP]], [[Cyclic guanosine monophosphate|cGMP]], and [[Calcium in biology|Ca<sup>2+</sup>]], that are located within the [[cytosol]] * '''[[Gases]]''': [[Signal transduction#Nitric oxide .28NO.29 as secondary messenger|nitric oxide (NO)]] and [[Carbon monoxide|carbon monoxide (CO)]], which can diffuse both through cytosol and across [[cell membrane|cellular membranes]]. These intracellular messengers have some properties in common: * They can be synthesized/released and broken down again in specific reactions by [[enzyme]]s or ion channels. * Some (like Ca<sup>2+</sup>) can be stored in special [[organelle]]s and quickly released when needed. * Their production/release and destruction can be ''localized'', enabling the cell to limit space and time of signal activity. ==Common mechanisms of secondary messenger systems== There are several different secondary messenger systems ([[Cyclic adenosine monophosphate|cAMP]] system, [[phosphoinositol]] system, and [[arachidonic acid]] system), but they all are quite similar in overall mechanism, though the substances involved in those mechanisms and effects are different. In all of these cases a [[neurotransmitter]] binds to a membrane-spanning [[receptor protein]] molecule. The binding of the neurotransmitter to the receptor changes the receptor and causes it to expose a binding site for a ''[[G-protein]]''. The G-protein (named for the [[guanosine diphosphate|GDP]] and [[guanosine triphosphate|GTP]] molecules that binds to it) is bound to the inner membrane of the cell and consists of three subunits: alpha, beta and gamma. The G-protein is known as the "[[Signal transduction|transducer]]." When the G-protein binds to the receptor, it becomes able to exchange a GDP (guanosine diphosphate) molecule on its alpha subunit for a GTP (guanosine triphosphate) molecule. Once this exchange takes place, the alpha subunit of the G-protein transducer breaks free from the beta and gamma subunits, all parts remaining membrane-bound. The alpha subunit, now free to move along the inner membrane, eventually contacts another membrane-bound [[protein]] - the "primary effector." The primary effector then has an action, which creates a signal that can diffuse within the cell. This signal is called the "secondary messenger." (The neurotransmitter is the first messenger.) The secondary messenger may then activate a "secondary effector" whose effects depend on the particular secondary messenger system. Calcium ions are responsible for many important physiological functions, such as in muscle contraction. It is normally bound to intracellular components even though a secondary messenger is a plasma membrane receptor. Calcium regulates the protein calmodulin, and, when bound to calmodulin, it produces an alpha helical structure. This is also important in muscle contraction. The enzyme [[phospholipase C]] produces [[diglyceride|diacylglycerol]] and [[inositol triphosphate]], which increases calcium ion permeability into the membrane. Active G-protein open up calcium channels to let calcium ions enter the plasma membrane. The other product of phospholipase C, diacylglycerol, activates [[protein kinase C]], which assists in the activation of cAMP(another second messenger). ==Examples== {| class="wikitable" | || '''[[Cyclic adenosine monophosphate|cAMP]] System''' || '''[[Phosphoinositol]] system''' || '''[[Arachidonic acid]] system''' || '''[[Cyclic guanosine monophosphate|cGMP]] System''' || - |- | ''[[Neurotransmitter]]s<BR>([[Receptor (biochemistry)|Receptor]])'' || [[Epinephrine]] ([[adrenergic receptor|α2, β1, β2]])<BR>[[Acetylcholine]] ([[Muscarinic acetylcholine receptor|M2]]) || [[Epinephrine]] ([[adrenergic receptor|α1]])<BR>[[Acetylcholine]] ([[Muscarinic acetylcholine receptor|M1, M3]]) || [[Histamine]] ([[Histamine receptor]]) || - || - |- | ''[[Hormone]]s'' || [[Adrenocorticotropic hormone|ACTH]], [[Atrial-natriuretic peptide|ANP]], [[Corticotropin-releasing hormone|CRH]], [[Calcitonin|CT]], [[Follicle-stimulating hormone|FSH]], [[Glucagon]], [[Human chorionic gonadotropin|hCG]], [[Luteinizing hormone|LH]], [[Melanocyte-stimulating hormone|MSH]], [[Parathyroid hormone|PTH]], [[Thyroid-stimulating hormone|TSH]] || [[angiotensin|AGT]], [[Gonadotropin-releasing hormone|GnRH]], [[Growth hormone-releasing hormone|GHRH]], [[Oxytocin]], [[Thyrotropin-releasing hormone|TRH]] || - || [[Atrial natriuretic peptide|ANP]], Nitric oxide || [[Insulin|INS]], [[Insulin-like growth factor|IGF]] |- | ''[[Signal transduction|Transducer]]'' || [[Heterotrimeric G protein|G<sub>s</sub>]] (β1, β2), [[Heterotrimeric G protein|G<sub>i</sub>]] (α2, M2) || [[Heterotrimeric G protein|G<sub>q</sub>]] || Unknown [[G-protein]] || - || - |- | ''Primary [[Effector (biology)|effector]]'' || [[Adenylyl cyclase]] || [[Phospholipase C]] || [[Phospholipase A]] || [[guanylate cyclase]] || [[receptor tyrosine kinase]] |- | ''Secondary messenger'' || cAMP ([[cyclic adenosine monophosphate]]) || IP<sub>3</sub> ([[inositol 1,4,5 triphosphate]]) and DAG ([[diglyceride|Diacylglycerol]]), both from [[Phosphatidylinositol (4,5)-bisphosphate|PIP2]] || [[Arachidonic acid]] || [[Cyclic guanosine monophosphate|cGMP]] || - |- | ''Secondary effector'' || [[protein kinase A]] || [[Ca++]] release (see [[calcium-binding protein]]) and PKC ([[protein kinase C]]) || [[5-Lipoxygenase]], [[12-Lipoxygenase]], [[cycloxygenase]] || [[protein kinase G]] || - |} ==External links== * {{MeshName|Second+Messenger+Systems}} * {{cite web|author= Kimball, J|title=Second messengers | url=http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html| accessmonthday=February 10 |accessyear=2006}} {{Cell signaling}} {{Signal transduction}} [[Category:Signal transduction]] [[de:Second Messenger]] [[es:Segundo mensajero]] [[fr:Messager secondaire]] [[he:שליח שניוני]] [[ja:セカンドメッセンジャー]] [[sl:Sekundarni obveščevalec]] [[fi:Toisiolähetti]] [[zh:第二信使]]