1. 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)

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

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

4. 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

5. Calcium Typically low in cytosol (why?) IP3 (inositol triphosphate) acts before Calcium FIGURE 11.13 Calcium ions are involved in muscle contractions and neurotransmitter release

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

7. 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

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