signal transductionsitabhra/meetings/school10/... · 2010-01-15 · -systems control:bidirectional...
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Signal Transduction
L S ShashidharaIISER Pune
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What is Signal Transduction?
It’s the process of converting signals into responses
i.e., receiving, interpreting, processing, amplifying and responding to information
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Why is Signal Transduction required?
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Forms of secreted molecules-mediated signaling
Autocrine Paracrine Endocrine
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Differences:
Distance: Paracrine signal travels short distances (few mm). A neurotransmitter travels 10-20nm. An endocrine signal (hormones) travel (in the circulation system) upto the entire length of the body. Thus, hormones are systemic effectors.
Timing: Neural signaling is brief: transmits and effects in lessthan a second. Endocrine signaling is longer: signals take more time to reach their targets, target cells take more time torespond, and signals are more stable.
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Components of Signal Transduction
SIGNAL
DISCRIMINATOR
TRANSDUCER
AMPLIFIER
RESPONSE
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Discriminator
Transducer
Amplifier
Effector
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Wnt signaling pathway has an essential role in growth and development of all most all organs and tissues of our body…
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EGFR Pathway
Ligand Spi/Vn/kek
EGFR
Ras
Raf
Dsor1
Rolled/MapK
Djun Pnt Yan
Target Genes
Csw
Dos
Drk
Sos
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Major Signal Transduction Pathways
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Evolution and Expansion of Intracellular Signaling
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Mitogen Activated Protein Kinase (MAPK) pathway : A typical example
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MAPK signalling cascade
How is pleiotropy in biological function achieved from a relatively simple biochemical pathway?(inherent to this is also the question of specificity)
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Amplitude and duration of the signal flux
Combinatorial integration of network crosstalk
Versatility of component function
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Combinatorial integration of network crosstalk
Versatility of component function
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Signal form rain results in umbrella opening
Model of signal transduction:monkey puzzle
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Is more better than less?
Why do MAPKs have a 3 tiered structure?
Does dual phosphorylation requirement of MAPKs for activation have an advantage?
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Feedback loops
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Scaffold proteins: localization/specificity
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The question of Integration: can Neural Networks help?
A neural network trained by evolution!Neural networks can be trained to recognize specific input patterns and generate corresponding specific output patterns
Thickness of arrows indicate connection weight
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Characteristics of a Robust system
-Bow-tie structure: core circuitary link input and output and is a point of fragility
-Modularity: divided into partially autonomous subsystems allowing diversification and damage containment
-Functional redundancy
-Systems control:bidirectional coupling of input and output via +/- feedback loops
-Pathway switching: extensive branching allows dynamic switching of signals to alternate routes
-Tolerance: ability to accumulate aberrations without significantly altering output
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Large interactive networks (incl. Neural Networks) display Robustness
ie, can maintain function despite external and internal perturbations
Robustness is essential for:
Appropriate communication
Generating appropriate response
Correct development
Cellular malfunction
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