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1. Cell Signaling
2. Cell Signaling Players
3. Signaling Paradigm
5. Signals Proteins
peptides
amino acids
lipids (ex/steriods)
gases (ex/NO)
nucleic acids
retinoic acid
6. Receptors Extracellular
Intracellular
8. Signaling Pathways Autocrine- signaling of self or to cells like self
Contact-Dependent-requires membrane contact between signaling and target cells
Paracrine-signaling in local environment
Synaptic-signaling in neuronal pathways
Endocrine-signaling at a distance
9. Autocrine
12. Contact dependent example:Gap junctions
13. Synaptic: Specificity achieved with direct contact
14. Endocrine:Specificity achieved with specific signals that are received by specific targets
15. More about signals. How do they work?
16. External signals are required for proliferation, differentiation, and even survival
17. The same signal can have different effects for different cell types
18. More about receptors. How do they work?
19. Receptors can be inside the cell. Enzymes that interact with dissolved gas signals
Nuclear Receptors
20. NO is a signal for smooth muscle relaxation
21. These signals bind nuclear receptors
23. Most of these types of signals are hormones (endocrine pathway). Nuclear receptors receive signal (bind signal) and then affect transcription of genes.
25. Signal is trapped inside the receptor by a helix that folds over in a conformational change
26. Receptors can be on the cell surface Three types of cell surface receptors
Ion-Channel-Linked
G-Protein-Linked
Enzyme-Linked
27. Types of Cell-Surface Receptors
29. 1. Ion-Channel-Linked Receptors
32. 2. G-Protein-Linked Receptors
33. G-Protein has three subunits. It is attached to plasma membrane.
34. Activation of a G-protein. Signaled receptor promotes GDP-GTP exchange. ?? complex or ? can then affect target (ion-channel or enzyme)
37. Some G-proteins work through 2nd Messenger cAMP
38. cAMP activates proteins
40. Gene transcription activated by cAMP signaling
41. G-protein linked receptor begins a pathway that increases Ca++ concentration in the cytosol via IP3
43. 3. Enzyme-Linked Receptors
45. Autophosphorylation depends on signals interacting with both receptor chains
47. Jak-Stat Pathway, representative enzyme -linked receptor pathway