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Signaling

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14 views24 pages

Signaling

Uploaded by

pradhansnehasis382
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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The study materials/presentations are solely meant for academic purposes and they can be reused,

reproduced, modified, and distributed by others for academic purposes only with proper
acknowledgements.
Increasing specificity of interaction- Intracellular Signaling Complexes Form at Activated
Receptors
One simple and effective strategy for enhancing the specificity of interactions between signaling
molecules is to localize them in the same part of the cell or even within large protein complexes,
thereby ensuring that they interact only with each other and not with inappropriate partners .

They can be executed in three ways


Molecular Biology of the Cell, Garland Science, 6th Edition
Molecular Biology of the Cell, Garland Science, 6th Edition
Molecular Biology of the Cell, Garland Science, 6th Edition
• One way to activate intracellular signaling proteins is to bring them together into close proximity
• One way of bringing receptors and intracellular signaling proteins together is to concentrate them in
a specific region of the cell.

• There are many types of interaction domains in signaling proteins like


Src homology 2 (SH2) domains – phosphorylated tyrosine
phosphotyrosine-binding (PTB) domains
Src homology 3 (SH3) domains - to short, proline-rich amino acid sequences.
pleckstrin homology (PH) domains bind to the charged head groups of specific phosphoinositides
Modular interactions and cell signalling

Molecular Biology of the Cell, Garland Science, 6th Edition


Signalling through GPCRs

Molecular Biology of the Cell, Garland Science, 6th Edition


When an extracellular signal molecule binds to a GPCR, the receptor undergoes a conformational change that enables it to
activate a trimeric GTP-binding protein (G protein), which couples the receptor to enzymes or ion channels in the
membrane.

In some cases, the G protein is physically associated with the receptor before the receptor is activated, whereas in others it
binds only after receptor activation.

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


https://www.youtube.com/watch?v=Glu_T6DQuLU

Molecular Biology of the Cell, Garland Science, 6th Edition


Some G Proteins Regulate the Production of Cyclic AMP- TSH, Vassopressin (Kidney)

Some G Proteins Signal Via Phospholipids- Vasopressin (Liver); acetylcholine (smooth Muscle, pancreas); thrombin (Platelet)

Some G Proteins Directly Regulate Ion Channels-olfaction, vision


Image: Molecular Biology of the Cell, Garland Science, 6th Edition
Image: Molecular Biology of the Cell, Garland Science, 6 th Edition
Vasopressin
Calcium- the all important ubiquitous second messenger

Ca2+-binding proteins help to


relay the cytosolic Ca2+ signal.
The most important is
calmodulin. Calmodulin
functions as a multipurpose
intracellular Ca2+ receptor,
governing many Ca2+-regulated
processes.

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


The olfactory receptors act through cAMP.

When stimulated by odorant binding they activate an olfactory-specific G protein (known as Golf), which in turn activates
adenylyl cyclase. The resulting increase in cAMP opens cyclic-AMP-gated cation channels, thereby allowing an influx of Na+,
which depolarizes the olfactory receptor neuron and initiates a nerve impulse that travels along its axon to the brain.

Vertebrate vision employs a similarly elaborate process but the crucial cyclic nucleotide is cyclic GMP
Signalling through enzyme coupled receptors:
1. Dimerization of receptors

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


2. Phosphorylated Tyrosines on RTKs
Serve as Docking Sites for
Intracellular Signaling Proteins
3. Proteins with SH2
Domains Bind to
Phosphorylated Tyrosines

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


4. The GTPase Ras Mediates Signaling by Most RTKs

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


5. Ras Activates a MAP Kinase Signaling Module

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition


Enzyme coupled reactions and how they work
RTK activation : https://www.youtube.com/watch?v=LT_ws4Xvj7M

MAPK/Erk : https://www.youtube.com/watch?v=thLsxvqDZ04
A simplified diagram of the
networks

Image: Molecular Biology of the Cell, Garland Science, 6 th Edition

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