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Cell Signaling Lect 2 - Copy

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Cell Signaling Lect 2 - Copy

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© © All Rights Reserved
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CELL SIGNALING

OR SIGNAL TRANSDUCTION

Lecture # 2
By Dr Seyyedha Abbas
2. Ion channels (Neurotransmitter linked)
 Directly control ion flux across the plasm membrane
 Two types - Both important in nervous system activity

1. Ligand gated:
 Activated when a specific molecule binds
 Example: acetylcholine receptor in postsynaptic cell

2. Voltage gated:
 Stimulus is electrical, not chemical
3. Cell surface membrane receptors
1. G-Protein – Coupled Receptors
2. Catalytic receptors
G-Protein – Coupled Receptors (GPCRs)
or 7TM receptors
 Largest family of cell surface receptors
 receptors that couple signal transduction to G-proteins
 Composed of a similar structure i.e.
1. An extra cellular ligand binding region
2. 7 Transmembrane helices (7TM receptor)
3. An intracellular domain that interacts with G-proteins
G-protein-linked receptors or seven-transmembrane
domain receptors, 7TM receptor
 G-Proteins:
 Bind Guanosine nucleotides (GTP & GDP)
 Two principal signal transduction pathways
involve the G protein-coupled receptors i.e.
 cAMP and phosphatidylinositol signal
pathways
 Trimeric proteins - 3 subunits – α, β , Ɣ
 Types:
1) Gs Stimulates and
2) Gi inhibits Adenylate cyclase.
 β & γ subunits are identical. α
subunits differ.
Catalytic Receptors
 Catalytic receptors, also known as Enzyme-linked
receptors, are a class of receptors that, upon ligand
binding, exhibit enzymatic activity
 cell surface receptor proteins – usually dimeric
 Transmembrane receptors having an inherent enzyme
activity as part of their structure
 Contain an extra cellular domain for ligand binding &
an intra cellular domain with specific enzyme activity
 Insulin receptors possess intrinsic tyrosine kinase
activity
 Directly linked to intracellular enzymes

 ligand binding and functional domains part of same

polypeptide chain

 Single transmembrane-spanning domain of 20-25


Receptors involve second messenger molecule

 Receptors are signal detector – bind Ligands

 Ligands bind to receptor located on plasma

membrane - Second messenger molecules---

intervene between the original message/signal and

ultimate effect on the cell - Cellular response


 Signaling often requires a rapid response and rapid
termination of the message, which may be achieved
by
a. degradation of the messenger or second messenger
b. the automatic G protein clock
c. Deactivation of signal transduction kinases by
phosphatases, or other means
Examples of second
messengers
1. cAMP: Glucagon, Calcitonin, CRH, ACTH, FSH,
ADH
2. cGMP: Atrial natriuretic factor (ANF), Nitric oxide
(NO)
3. Calcium or phosphatidylinositol or both: ADH,
Oxytocin, TRH, Gastrin, Angiotensin II
4. Kinase/ phosphatase cascade: Insulin, Growth
hormone, Insulin like growth factor (IGF), Prolactin
Types Of Second Messenger pathways

1) Adenylate Cyclase pathway

2) Calcium/ phosphatidylinositol pathway

3) Guanylate cyclase pathway

4) Kinase / phosphatase pathway


1) Adenylate Cyclase pathway

Adenylate Cyclase:
a membrane bound enzyme that converts ATP to
3/,5/- cyclic adenosine monophosphate (c AMP)
Mechanism of action of Adenylate Cyclase
pathway
Mechanism of action of Adenylate Cyclase pathway

ECF
which converts ATP to cAMP

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