ORGANIZATION OF SAGNAL TRANSDUCTON PATHWAY : ORGANIZATION OF SAGNAL TRANSDUCTON PATHWAY Seminar presented by
P.G. DEPT OF PHARMACEUTICAL CHEMISTRY
LUQMAN COLLEGE OF PHARMACY
GULBARGA – 585 102. RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE ORGANISATION OF SIGNAL TRANSDUCTION PATHWAY : ORGANISATION OF SIGNAL TRANSDUCTION PATHWAY What is signal transduction:- It is any process by which a cell converts one kind of signal in to another.
Signal transduction often involves a sequence of biochemical reaction inside cell which are carried out by enzyme.
SLOWER PROCESS ARE RARELY REFFERED TO AS A SAGNAL TRANSDUCTION TYPES OF SIGNALS : TYPES OF SIGNALS A]EXTRACELLULAR-
Signal transduction usually involves the binding of extracellular signaling molecules to receptors that face outwards from the membrane &trigger events inside.
Receptor typically responds to the specific molecules or ligand for which they have affinity.
Most extrcellular chemicals signals are hydrophilic and are unable to penetrate in to lipid membrane , a common kind of extracellular signal is nutrient.
This ligand responsible for sensation of smell & taste. B] INTRACELLULAR : B] INTRACELLULAR It triggered by the external signal are considerd distinct from the event of transduction”it self” refers only the step that converts the extracellular signal to an intracellular one.
It is present in eukaryotic cell
It is accomplished by extracellular signaling & takes place in multicellular organism within endocrinology. C] HORMONES : C] HORMONES Most of the molecules enable signaling b/w cells or tissues within an individuals are known as “hormones”.
following steps are involved in signal transduction-
2.Storage & secreation
3.Transport to target cell
4.Recognition of hormones receptors protien
5.Relay an emplification of signal
6.Removal of the hormones Slide 6: Hormones and other signaling molecules exit the sending cell by exocytosis or membrane transport.
Its recipients may be of one type or several type.
As in the case of insulin , which triggers the systemic effects. CELL SURFACE RECEPTORS : CELL SURFACE RECEPTORS Most extracellular molecules are hydrophilic and are able to activate receptor proteins only on the surface of the target cell.
These receptor act’s as signal transducers an alter the behavior of target cell. TYPES OF CELL SURFACE RECEPTORS : TYPES OF CELL SURFACE RECEPTORS 1)Ion channel linked receptor-
They are open or closed in response to the binding of neurotransmitter.
2)G-Protein coupled receptor-
It act’s by enzyme or ion channels via trimeric GTP-binding proteins.
3)Enzyme linked receptor-
Act directly as enzyme or are associated with enzyme.
The enzymes are usually protein kinase that phosphorylate specific protein in target cell. G-PROTEIN LINKED RECEPTORS : G-PROTEIN LINKED RECEPTORS It is largest family of cell surface receptors.
It is Guanine-nucleotide binding proteins.
They mediate cellular response by signaling molecules includes hormones,neurotransmitter,and local mediaters.
At least 9 distinct G-protein linked receptors are mediated by adrenaline.
5 or more are activated by acetylcholine.
And least 15 by serotonin. structure : structure All of the G-protein receptors whose amino acid sequence are known from DNA sequencing.
It consist of a single polypeptide chain of up to 1100 residues.
It consist of 3 subunits alpha , beta and gamma.
Guanine bind to the alpha subunit which has enzymic activity ,catalyzing the conversion of GTP to GDP by GTPase enzyme.
All three subunits are anchored to the membrane through a fatty acid chain coupled to G-protein through a reaction known as PRENYLATION. G-Protein Signal By regulating The Production Of C-AMP : G-Protein Signal By regulating The Production Of C-AMP Many extracellular signal molecules work by increasing cyclic AMP& increase the activity of adenyl cyclase(AC) rather than decrease the activity of phosphodiesterase.
All receptors that act via C-AMP are coupled to a stimulatory G-protein which activate AC & thereby increase C-AMP concentration.
G-proteins are targets for some medically imp bacterial toxins.
Ex-pertussis toxin which is made by the bacterium that cause pertussis(whooping cough) catalyse the ADP ribosylation of alpha subunit of Gi preventing interacting with receptors.
These toxins are widely used as tools to determine weather a cell response to a signal is mediated by Gs or Gi. ENZYME LINKED RECEPTORS : ENZYME LINKED RECEPTORS It is transmembrane proteins with their ligand binding on the outer surface of the plasma membrane.
These signal proteins are often collectively called “GROWTH FACTORS”.
These also to mediate direct,rapid effects on cytoskeleton controlling the way a cell moves & changes it’s shape.
The largest group of receptors which intrinsic enzymatic activity consist of cell surface protein kinase,which exert regulatory effects by phosphorylating at the inner face of plasma membrane. Slide 13: Protein phosphorylation can alter the biochemical activities of effector proteins.
Most receptors that arte protein kinases phosphorylate tyrosine residue in their substrates.this receptor inculudes INSULIN & divers polypeptides that direct growth or differentiation such as Epidermal Growth Factor & Nerve Growth Factor.
A few receptor protein kinases phosphorylation arginine or threonine residues. GAUNYLYL CYCLASE RECEPTOR GENERATE C-GMP DIRECTLY : GAUNYLYL CYCLASE RECEPTOR GENERATE C-GMP DIRECTLY These are single pass transmembrane proteins with an extra cellular binding site for signal molecules & an intracellular guanylyl cylclase catalytic domain.
Binding of signal molecules activates cyclase domain to produce C-GMP & activates protein kinase which phosphorylate specific protein i.e.serine or threonine.
Signal molecules use guanylyl cyclase receptor are natriutric peptides(NPs) secreted signal peptides that regulate salt&water balance. Slide 15: There are several type’s of NPs including atrial natriaretic peptides(ANP) and brain natriaretic peptides(BNP).
Muscle cells in atrium of the heart secreat ANP when B.P. rises.
ANP stimulates kidney to secreate Na & water and induce blood vessels walls to relax, hence lower the B.P.