WordNet

transfer an employee to a different, temporary assignment; "The officer was seconded for duty overseas"
a 60th part of a minute of arc; "the treasure is 2 minutes and 45 seconds south of here" (同)arcsecond
1/60 of a minute; the basic unit of time adopted under the Systeme International dUnites (同)sec, s
following the first in an ordering or series; "he came in a close second"
a speech seconding a motion; "do I hear a second?" (同)secondment, endorsement, indorsement
the official attendant of a contestant in a duel or boxing match
coming next after the first in position in space or time or degree or magnitude (同)2nd, 2d
give support or ones approval to; "Ill second that motion"; "I cant back this plan"; "endorse a new project" (同)back, endorse, indorse
in the second place; "second, we must consider the economy" (同)secondly
a part or voice or instrument or orchestra section lower in pitch than or subordinate to the first; "second flute"; "the second violins"
a person who carries a message (同)courier

PrepTutorEJDIC

《通例the~》『第2の』,2番目(2度目)の《略》『2nd,sec.』) / 《A~+名で》『もう一つの』,別の / 一級(最上)のものに次ぐ,二流の / (自動車の変速機の)第2速の / 低音(声)部の,第2の / 〈C〉《the~》『2番目の人』(『物,事』) / 〈U〉《the~》(月の)『第2日』 / 〈C〉(ボクシングの)セコンド;(決闘などの)介添人;(一般に)援助者 / 〈C〉《しばしば複数形で》二流品（ボタンが取れているなど、比較的小さな問題のある格安の服）・〈C〉〈U〉2度音程,第2音(声)部 / 〈U〉(自動車の変速機の)第2速,セカンド[ギア] / 《the~》《最上級の形容詞を伴って》第2に,2番目に / 第2位で,2等で / 〈提案・動議など〉‘に'賛成する,‘を'支持する / …‘を'援助する,後援する,激励する;(ボクシングで)…‘の'セコンドを務める
(時間・角度の)『秒』 / 《単数形で》『瞬間』(moment)
『使いの者』,走り使い;(電報・郵便物・小包の)配達人;(公文書の)送達吏
（食事の）お代わり（second helping）・欠陥のある格安の衣料

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/10 07:53:49」(JST)

wiki en

Second messengers are intracellular signaling molecules released by the cell to trigger physiological changes such as proliferation, differentiation, migration, survival, and apoptosis. Secondary messengers are therefore one of the initiating components of intracellular signal transduction cascades. Examples of second messenger molecules include Cyclic AMP, Cyclic GMP, Inositol Triphosphate, Diacylglycerol, and Calcium. The cell releases second messenger molecules in response to exposure to extracellular signals - the First messengers. First Messengers are extracellular substances that include peptide hormones such as epinephrine, growth factors, and neurotransmitters such as serotonin. Because hormones and neurotransmitters typically comprise biochemically hydrophilic molecules, first messengers may not physically cross the phospholipid bilayer cell membrane to initiate changes within the cell directly. This functional limitation necessitates the cell to devise signal transduction mechanisms to transduce first into second messengers, so that the extracellular signal may be propagated intracellularly. An important feature of the second messenger signaling system is that second messengers may be coupled downstream to multi-cyclic kinase cascades to greatly amplify the strength of the original first messenger signal.^[1]^[2] For example, Ras.GTP signals link with the Mitogen Activated Protein Kinase (MAPK) cascade to amplify the allosteric activation of proliferative transcription factors such as Myc and CREB.

Earl Wilbur Sutherland, Jr., discovered second messengers, for which he won the 1971 Nobel Prize in Physiology or Medicine. Sutherland saw that epinephrine would stimulate the liver to convert glycogen to glucose (sugar) in liver cells, but epinephrine alone would not convert glycogen to glucose. He found that epinephrine had to trigger a second messenger, cyclic AMP, for the liver to convert glycogen to glucose.^[3] The mechanisms were worked out in detail^[4]^[5] by Martin Rodbell and Alfred G. Gilman, who won the 1994 Nobel prize.

Secondary messenger systems can be synthesized and activated by enzymes, for example, the cyclases that synthesize cyclic nucleotides, or by opening of ion channels to allow influx of metal ions, for example Ca²⁺ signaling. These small molecules bind and activate protein kinases, ion channels, and other proteins, thus continuing the signaling cascade.

Types of secondary messenger molecules

There are three basic types of secondary messenger molecules:

Hydrophobic molecules: water-insoluble molecules such as diacylglycerol, and phosphatidylinositols, which are membrane-associated and diffuse from the plasma membrane into the intermembrane space where they can reach and regulate membrane-associated effector proteins
Hydrophilic molecules: water-soluble molecules, such as cAMP, cGMP, IP₃, and Ca²⁺, that are located within the cytosol
Gases: nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S) which can diffuse both through cytosol and across cellular membranes.

These intracellular messengers have some properties in common:

They can be synthesized/released and broken down again in specific reactions by enzymes or ion channels.
Some (such as Ca²⁺) can be stored in special organelles 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

General Schematic of Second Messenger Mechanism

There are several different secondary messenger systems (cAMP system, phosphoinositol system, and arachidonic acid system), but they all are quite similar in overall mechanism, although the substances involved and overall effects can vary.

In most cases, a ligand binds to a membrane-spanning receptor protein molecule. The binding of a ligand to the receptor causes a conformation change in the receptor. This conformation change can affect the activity of the receptor and result in the production of active second messages.

In the case of G protein-coupled receptors, the conformation change exposes a binding site for a G-protein. The G-protein (named for the GDP and GTP molecules that bind 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 "transducer."

When the G-protein binds with 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 "second (or secondary) messenger." (The ligand 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 one type of second messengers and are responsible for many important physiological functions including muscle contraction, fertilization and neurotransmitter release. The ions are normally bound or stored in intracellular components (such as the endoplasmic reticulum) and can be released during signal transduction. The enzyme phospholipase C produces diacylglycerol and inositol trisphosphate, 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

	cAMP System	Phosphoinositol system	Arachidonic acid system	cGMP System	Tyrosine kinase system
First Messenger: Neurotransmitters (Receptor)	Epinephrine (α2, β1, β2) Acetylcholine (M2)	Epinephrine (α1) Acetylcholine (M1, M3)	Histamine (Histamine receptor)	-	-
First Messenger: Hormones	ACTH, ANP, CRH, CT, FSH, Glucagon, hCG, LH, MSH, PTH, TSH	AGT, GnRH, GHRH, Oxytocin, TRH	-	ANP, Nitric oxide	INS, IGF, PDGF
Signal Transducer	GPCR/G_s (β1, β2), G_i (α2, M2)	GPCR/G_q	Unknown G-protein	-	RTK
Primary effector	Adenylyl cyclase	Phospholipase C	Phospholipase A	guanylate cyclase	RasGEF (Grb2-Sos)
Second messenger	cAMP (cyclic adenosine monophosphate)	IP3; DAG; Ca2+	Arachidonic acid	cGMP	Ras.GTP (Small G Protein)
Secondary effector	protein kinase A	PKC; CaM	5-Lipoxygenase, 12-Lipoxygenase, cycloxygenase	protein kinase G	MAP3K (c-Raf)

References

^ Kimball, J. "Second messengers".
^ Second Messenger Systems at the US National Library of Medicine Medical Subject Headings (MeSH)
^ Reece, Jane; Campbell, Neil (2002). Biology. San Francisco: Benjamin Cummings. ISBN 0-8053-6624-5.
^ The Discovery of G Proteins
^ Signal Transduction in Cells, Nobelprize.org

External links

Kimball, J. "Second messengers". Retrieved February 10, 2006.
Animation: Second Messenger: cAMP

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English Journal

The role of the globin-coupled sensor YddV in a mature E. coli biofilm population.

Donné J1, Van Kerckhoven M2, Maes L2, Cos P2, Dewilde S3.
Biochimica et biophysica acta.Biochim Biophys Acta.2016 Jul;1864(7):835-9. doi: 10.1016/j.bbapap.2016.04.005. Epub 2016 Apr 12.
Biofilm-associated infections are hard to treat because of their high antibiotic resistance and the presence of a very persistent subpopulation of bacteria. The second messenger molecule cyclic di-guanosine monophosphate (c-di-GMP) plays a very important role in this biofilm physiology. Here, we eva
PMID 27083533

Studying mechanisms of cAMP and cyclic nucleotide phosphodiesterase signaling in Leydig cell function with phosphoproteomics.

Golkowski M1, Shimizu-Albergine M1, Suh HW1, Beavo JA2, Ong SE3.
Cellular signalling.Cell Signal.2016 Jul;28(7):764-78. doi: 10.1016/j.cellsig.2015.11.014. Epub 2015 Nov 28.
Many cellular processes are modulated by cyclic AMP and nucleotide phosphodiesterases (PDEs) regulate this second messenger by catalyzing its breakdown. The major unique function of testicular Leydig cells is to produce testosterone in response to luteinizing hormone (LH). Treatment of Leydig cells
PMID 26643407

Protein-protein interactions of PDE4 family members - Functions, interactions and therapeutic value.

Klussmann E1.
Cellular signalling.Cell Signal.2016 Jul;28(7):713-8. doi: 10.1016/j.cellsig.2015.10.005. Epub 2015 Oct 21.
The second messenger cyclic adenosine monophosphate (cAMP) is ubiquitous and directs a plethora of functions in all cells. Although theoretically freely diffusible through the cell from the site of its synthesis it is not evenly distributed. It rather is shaped into gradients and these gradients are
PMID 26498857

Japanese Journal

活性酸素による多階層シグナル伝達機構とレドックス恒常性制御

赤池孝章
YAKUGAKU ZASSHI 134(4), 515-519, 2014
… This potent cardioprotective effect resulted from strong suppression of H-Ras signaling activated by electrophilic stimulation with 8-nitro-cGMP functioning as a second messenger for the redox signaling induced by NO and ROS. …
NAID 130003391199

cAMP Signaling Affects Irreversible Attachment During Biofilm Formation by Pseudomonas aeruginosa PAO1

Ono Kaori,Oka Rie,Toyofuku Masanori,Sakaguchi Ayane,Hamada Masakaze,Yoshida Shiomi,Nomura Nobuhiko
Microbes and Environments, 2014
… The control of cell attachment to surfaces is one of the critical processes that determine this transition.Environmental signals are typically relayed to the cytoplasm by second messenger systems. … We here demonstrated that the second messenger, cAMP, regulated the attachment of cells. …
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The c-di-GMP recognition mechanism of the PilZ domain of bacterial cellulose synthase subunit A

Fujiwara Takaaki,Komoda Keisuke,Sakurai Naofumi,Tajima Kenji,Tanaka Isao,Yao Min
Biochemical and Biophysical Research Communications 431(4), 802-807, 2013-02-22
… In some Proteobacteria and Firmicutes such as Pseudomonas aeruginosa, Vibrio cholerae, Xanthomonas campestris, and Clostridium difficile, cyclic dimeric guanosine monophosphate (c-di-GMP) is known to regulate cellular processes, including motility, biofilm formation, and virulence, as a second messenger. …
NAID 120005228632

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