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The effects of extracellular signals can also be amplified by enzymatic cascades. At the initiation of the signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can activate many copies of a component of the signaling cascade, which amplifies the signal.

Methods of intracellular signaling

The induction of a signaling pathway depends on the modification of a cellular component by an enzyme. There are numerous enzymatic modifications that can occur, and they are recognized in turn by the next component downstream. The following are some of the more common events in intracellular signaling.

Observe an animation of cell signaling at this site .

Phosphorylation

One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group (PO 4 –3 ) to a molecule such as a protein in a process called phosphorylation. The phosphate can be added to a nucleotide such as GMP to form GDP or GTP. Phosphates are also often added to serine, threonine, and tyrosine residues of proteins, where they replace the hydroxyl group of the amino acid ( [link] ). The transfer of the phosphate is catalyzed by an enzyme called a kinase    . Various kinases are named for the substrate they phosphorylate. Phosphorylation of serine and threonine residues often activates enzymes. Phosphorylation of tyrosine residues can either affect the activity of an enzyme or create a binding site that interacts with downstream components in the signaling cascade. Phosphorylation may activate or inactivate enzymes, and the reversal of phosphorylation, dephosphorylation by a phosphatase, will reverse the effect.

Molecular structures of phosphoserine, phosphothreonine and phosphotyrosine are shown. In each molecule, a phosphate is attached to an oxygen on the amino acid.
In protein phosphorylation, a phosphate group (PO 4 -3 ) is added to residues of the amino acids serine, threonine, and tyrosine.

Second messengers

Second messengers are small molecules that propagate a signal after it has been initiated by the binding of the signaling molecule to the receptor. These molecules help to spread a signal through the cytoplasm by altering the behavior of certain cellular proteins.

Calcium ion is a widely used second messenger. The free concentration of calcium ions (Ca 2+ ) within a cell is very low because ion pumps in the plasma membrane continuously use adenosine-5'-triphosphate (ATP) to remove it. For signaling purposes, Ca 2+ is stored in cytoplasmic vesicles, such as the endoplasmic reticulum, or accessed from outside the cell. When signaling occurs, ligand-gated calcium ion channels allow the higher levels of Ca 2+ that are present outside the cell (or in intracellular storage compartments) to flow into the cytoplasm, which raises the concentration of cytoplasmic Ca 2+ . The response to the increase in Ca 2+ varies, depending on the cell type involved. For example, in the β-cells of the pancreas, Ca 2+ signaling leads to the release of insulin, and in muscle cells, an increase in Ca 2+ leads to muscle contractions.

Another second messenger utilized in many different cell types is cyclic AMP (cAMP)    . Cyclic AMP is synthesized by the enzyme adenylyl cyclase from ATP ( [link] ). The main role of cAMP in cells is to bind to and activate an enzyme called cAMP-dependent kinase (A-kinase) . A-kinase regulates many vital metabolic pathways: It phosphorylates serine and threonine residues of its target proteins, activating them in the process. A-kinase is found in many different types of cells, and the target proteins in each kind of cell are different. Differences give rise to the variation of the responses to cAMP in different cells.

Cyclic AMP is made from ATP by the enzyme adenylyl cyclase. In the process, a pyrophosphate molecule composed of two phosphate residues is released. Cyclic AMP gets its name because the phosphate group is attached to the ribose ring in two places, forming a circle.
This diagram shows the mechanism for the formation of cyclic AMP (cAMP). cAMP serves as a second messenger to activate or inactivate proteins within the cell. Termination of the signal occurs when an enzyme called phosphodiesterase converts cAMP into AMP.

Present in small concentrations in the plasma membrane, inositol phospholipids are lipids that can also be converted into second messengers. Because these molecules are membrane components, they are located near membrane-bound receptors and can easily interact with them. Phosphatidylinositol (PI) is the main phospholipid that plays a role in cellular signaling. Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP 2 ).

The enzyme phospholipase C cleaves PIP 2 to form diacylglycerol (DAG)    and inositol triphosphate (IP 3 )    ( [link] ). These products of the cleavage of PIP 2 serve as second messengers. Diacylglycerol (DAG) remains in the plasma membrane and activates protein kinase C (PKC), which then phosphorylates serine and threonine residues in its target proteins. IP 3 diffuses into the cytoplasm and binds to ligand-gated calcium channels in the endoplasmic reticulum to release Ca 2+ that continues the signal cascade.

The molecular structures of PIP_2, DAG, and IP_3 are shown. PIP_2 is a phospholipid that is cleaved by phospholipase C to form DAG, which has a long hydrophobic tail, and IP_3, a ring structure with three phosphates attached.
The enzyme phospholipase C breaks down PIP 2 into IP 3 and DAG, both of which serve as second messengers.

Section summary

Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that conveys the signal through the cell is called a signaling pathway or cascade. Signaling pathways are often very complex because of the interplay between different proteins. A major component of cell signaling cascades is the phosphorylation of molecules by enzymes known as kinases. Phosphorylation adds a phosphate group to serine, threonine, and tyrosine residues in a protein, changing their shapes, and activating or inactivating the protein. Small molecules like nucleotides can also be phosphorylated. Second messengers are small, non-protein molecules that are used to transmit a signal within a cell. Some examples of second messengers are calcium ions (Ca 2+ ), cyclic AMP (cAMP), diacylglycerol (DAG), and inositol triphosphate (IP 3 ).

Art connections

[link] In certain cancers, the GTPase activity of the RAS G-protein is inhibited. This means that the RAS protein can no longer hydrolyze GTP into GDP. What effect would this have on downstream cellular events?

[link] ERK would become permanently activated, resulting in cell proliferation, migration, adhesion, and the growth of new blood vessels. Apoptosis would be inhibited.

Questions & Answers

Is there any normative that regulates the use of silver nanoparticles?
Damian Reply
what king of growth are you checking .?
Renato
What fields keep nano created devices from performing or assimulating ? Magnetic fields ? Are do they assimilate ?
Stoney Reply
why we need to study biomolecules, molecular biology in nanotechnology?
Adin Reply
?
Kyle
yes I'm doing my masters in nanotechnology, we are being studying all these domains as well..
Adin
why?
Adin
what school?
Kyle
biomolecules are e building blocks of every organics and inorganic materials.
Joe
anyone know any internet site where one can find nanotechnology papers?
Damian Reply
research.net
kanaga
sciencedirect big data base
Ernesto
Introduction about quantum dots in nanotechnology
Praveena Reply
what does nano mean?
Anassong Reply
nano basically means 10^(-9). nanometer is a unit to measure length.
Bharti
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Damian Reply
absolutely yes
Daniel
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Maciej
characteristics of micro business
Abigail
for teaching engĺish at school how nano technology help us
Anassong
Do somebody tell me a best nano engineering book for beginners?
s. Reply
there is no specific books for beginners but there is book called principle of nanotechnology
NANO
what is fullerene does it is used to make bukky balls
Devang Reply
are you nano engineer ?
s.
fullerene is a bucky ball aka Carbon 60 molecule. It was name by the architect Fuller. He design the geodesic dome. it resembles a soccer ball.
Tarell
what is the actual application of fullerenes nowadays?
Damian
That is a great question Damian. best way to answer that question is to Google it. there are hundreds of applications for buck minister fullerenes, from medical to aerospace. you can also find plenty of research papers that will give you great detail on the potential applications of fullerenes.
Tarell
what is the Synthesis, properties,and applications of carbon nano chemistry
Abhijith Reply
Mostly, they use nano carbon for electronics and for materials to be strengthened.
Virgil
is Bucky paper clear?
CYNTHIA
carbon nanotubes has various application in fuel cells membrane, current research on cancer drug,and in electronics MEMS and NEMS etc
NANO
so some one know about replacing silicon atom with phosphorous in semiconductors device?
s. Reply
Yeah, it is a pain to say the least. You basically have to heat the substarte up to around 1000 degrees celcius then pass phosphene gas over top of it, which is explosive and toxic by the way, under very low pressure.
Harper
Do you know which machine is used to that process?
s.
how to fabricate graphene ink ?
SUYASH Reply
for screen printed electrodes ?
SUYASH
What is lattice structure?
s. Reply
of graphene you mean?
Ebrahim
or in general
Ebrahim
in general
s.
Graphene has a hexagonal structure
tahir
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Cied
what is biological synthesis of nanoparticles
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how did you get the value of 2000N.What calculations are needed to arrive at it
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Source:  OpenStax, Genetics and evolution. OpenStax CNX. Aug 07, 2014 Download for free at https://legacy.cnx.org/content/col11595/1.2
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