1. CHAPTER 11 cell signaling
Local regulators
Ex) growth factors – paracrine signaling and synaptic signaling
Long distance signaling
- Hormones (insulin, ethylene)
- nervous system

2. 3 stages of signaling
Earl Sutherland (1971) Epinephrine and glycogen breakdown
Reception – binding to signal receptor
Transduction-often a series of changes (signal transduction pathway)
Response-end result – a specific cellular response

3. Receptor types I. Bound to plasma membrane G protein couple receptors
Receptor Tyrosine Kinases
Ion channel receptors
II. Intracellular
Located in cytosol or nucleus
require hydrophobic or small messengers
Steroid hormones, thyroid hormones, NO

4. Membrane receptors up close
G Protein-Coupled receptors
widespread, very common, involved with neurotransmitters(nervous), many hormones (epinephrine), and embryonic development
Involves G protein and GTP

5. G protein (cytoplasmic side) is off when bound to GDP
Ligand binds to extracellular side of receptor
Receptor is actived (shape) and binds to G protein
GTP replaces GDP on G protein
G protein binds to and activates an enzyme
G protein hydrolyzes GTP to GDP (GTPase) and returns to start

6. Receptor Tyrosine Kinases
kinases transfer phosphate groups
Involved with enzymatic activity
Ex. Growth hormone binding/response

7. Individual receptor tyrosine kinase proteins bind a signaling molecule (ligand)
Tyrosine kinase proteins form a dimer
This activates the kinase region of each, and each tyrosine kinase phosphorylates its tyrosines via ATP
Once activated, it is recognized by relay proteins in cell and binds them
Often activates multiple pathways

8. Ion Channel Receptors
Involves gated responses involving ion flow
Ex) neurotransmitters (ligands) and neurons (action potentials)
Ions flowing across membranes create currents

9. Ligand binds to channel receptor while receptor is in closed conformation
Receptor changes shape to open gate
Very specific ion(s) begin to flow down their electrochemical gradient
This flow of ions affects cell function
Ligand dissociates, ending the process

10. Intracellular receptor model
Results in gene expression (ex. Testosterone effects)
Steroid hormone passes through plasma membrane and binds to receptor protein in cytoplasm
Activated receptor protein enters the nucleus and acts as a transcription factor for a particular gene

11. Cascading……….
Can greatly amplify the signal to numerous molecules at each step *usually involves “phosphorylating” proteins a)protein kinase – transfers phosphates to other proteins(targeting serine or threonine)

12. b) Protein phosphatase – de-phosphorylates proteins, making them available again and terminating the signal.

13. Second Messengers
Involves small, non-protein , water soluble molecules or ions
Focus: cyclic AMP (cAMP) and Calcium(Ca++)

14. cAMP figure 11.10/11.11 1. Epinephrine binds to receptor protein
2. Receptor activates “adenylyl cyclase” which converts many ATP to cAMP
3. cAMP is short lived due to “phosphodiesterase”, which converts cAMP to AMP
4. Some G protein pathways can inhibit adenylyl cyclase

15. Calcium
Typically low in cytosol (why?) IP3 (inositol triphosphate) acts before Calcium FIGURE Calcium ions are involved in muscle contractions and neurotransmitter release

16. FINE tuning
Signal Amplification – a small amount of signaling molecule can cause large changes
Different responses to same signaling molecule (epinephrine)
Signaling efficiency – scaffolding proteins – pathways are often complex, not linear(11.18)
Termination is necessary

17. APOPTOSIS
-programmed cell death via “digestion” (internally and externally)
Signal can be external (from other cells) or internal from nucleus or ER
Proteins for such events are always present, but inactive
Caspases are proteases of apoptosis

18. C. elegans (nematode) ced-3 and Ced-4 genes for appropriate apoptosis proteins

19. Learning outcome
Objectives: 1) students will be able to relate cell differentiation and specialization to different cellular responses to a particular ligand. 2) Students will be able to discuss various mechanisms by which cells can communicate with other cells via signaling molecules.

20. Multiple choice
One major characteristic of cell signaling is that the pathway must be able to be “turned on and shut off” when needed. Which pathway involves an activation mechanism not initiated by the binding of a ligand to and external cellular receptor?
a) the phosphorylation of tyrosines
b) the opening and closing of voltage regulated ion channels
c) reception of a hormone to form a transcription factor
d) the binding of GTP to activate a G protein

21. Open Response a) Discuss the three stages of “cell signaling.”
b) Explain how just one particular ligand can ultimately stimulate different types of body cells to respond in very different ways. Also, describe why some body cells might not respond at all to a given ligand.