1. Basics of Signal Transduction
Ebaa M Alzayadneh, PhD

2. What is signal transduction?

3. Cell signaling
The science of understanding how individual cells sense their environments and respond to stimuli...
how so many functionally different cells
can come from one fertilized egg?

5. Signaling is responsible for how cells can respond to their
environment and how they can differentiate or change over time

6. Objectives Know the basics concepts of signal transduction
Know specific mechanisms
Membrane Receptor mediated (very diverse group)
G-protein coupled
Ion channel-linked
Enzyme linked (example will be Receptor Tyrosine Kinases)
Receptors that link to proteases
Non-membrane receptor mediated pathways
NO pathway
Steroid hormone receptors

7. Communication by Extracellular Signaling usually involves:
1. Synthesis of the signaling molecule by the signaling cell
2. Release of the signaling molecule by the signaling cell
3. Transport of the signal to the target cell
4. Binding of the signal by a specific receptor protein 􀃆 conformational
change
5. Initiation of intracellular signal-transduction pathways by the activated
receptor
6. A change in cellular metabolism, function, structure, or development
triggered immediately by the receptor-signal complex
7. Usually deactivation of the receptor
8. Removal of the signal, which usually terminates the cellular response
-Additionally:
Receptors also exist that bind and react to metabolites (oxygen, sugar, NO....)or physical stimuli (touch, light, heat....) In which case step 4-8 still apply

9. Basic concepts
The same signal can induce different responses in different target cells
Different combinations of signals induce different responses
Responses can be fast or slow
Signals are mediated by two types of receptors
Signals are relayed and amplified

10. Signals get translated into cellular responses or
changes in gene expression

11. Not all of the receptor needs to be bound to induce a response

12. Signals can act locally or at a distance

13. Basic types of signaling

16. The same signal can produce a different response
in different targets

17. Different combinations of signals induce different responses

18. Responses can be fast or slow

19. Signals are mediated by two types of receptors

20. Signals are amplified

21. Major components of signaling pathways
Signals
Receptors
G-proteins
Protein kinases
Protein phosphatases
Second messenger producing components

22. Signaling is very conserved
The same machinery is used in many different signaling pathways
Different cell types will use the same machinery for different purposes

23. Proteins involved in signaling are conserved
Human, C. elegans, drosophila; 1500 genes in common; 28% of this common set are involved in Signal transduction, 33% are of unknown function
Proteins involved in signaling are conserved

24. Extracellular and intracellular
What are signals?
Extracellular and intracellular

25. Extracellular signals
Physical
Light, heat, touch, magnetic, electric
Chemical
Growth factors, hormones, nutrients, environmental cues
Typically these initiate an action

26. Receptors determine response
No receptor - no response

27. Intracellular signals
We will focus on intracellular signals
Secondary messengers
Other types of signals (will see later)
Typically these propagate or amplify an extracellular signal
Some mediate internal signals
Examples of hormones signaling pathways

28. Small organic molecules as signals
Calcium can also be a signal

29. Other types of signals Changes in phosphorylation states
Changes in ionic (Vm) composition
Changes in what a protein is bound to
Changes in protein structure

30. Extracellular signal receptors
And the machinery that transmits their signals

31. Membrane bound receptors come in different forms