1. Cell to cell communication = Cell signalling Ligand (ex insulin, epinephrine)→ Receptor → G protein (GDP to GTP) → adenylyl cyclase→ cAMP (second messenger and signal amplification) → activate protein kinase (several kinds)→ phosphorylate a protein(s) (result in an effect) Involves a signal molecule secreted from one cell that interacts with receptors on a second cell. The secreted molecule could be a hormone, neurotransmitter, histamine or other substance that either acts locally (paracrine), moves through the bloodstream to another organ (endocrine) or is released by a neuron (synaptic). The molecule binding with the receptor initiates a sequence of events mediated by a g protein that that results in a biological effect. The type of effect depends on the secreted molecule and the cell type; some molecules can have different effects on different cells – the question is how?

3. Gap junction between two cells (ex muscle) to promote exchange of materials

4. Signals can either interact at the surface of the cell (protein hormones, growth factors) or inside the cell (steroid hormones, NO)

5. Different modes of signalling; we will focus on endocrine for now

8. http://www.prism.gatech.edu/~gh19/b1510/si gnal.htm http://www.biology.arizona.edu/cell_bio/probl em_sets/signaling/overview.html Good tutorials http://users.rcn.com/jkimball.ma.ultranet/Biol ogyPages/C/CellSignaling.html This one is a bit advanced but lists all known kinds of cell signalling

9. http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter17/animation__sec ond_messenger__camp.html Good basic introduction to G proteins and cAMP http://highered.mcgraw-hill.com/olc/dl/120069/bio08.swf Signal amplification http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html G protein mediated work of epimephrine and glycogen very good http://www.youtube.com/watch?v=iGb93jCKVXs&fe ature=related cAMP and kinase example http://highered.mcgraw-hill.com/olc/dl/120069/bio06.swf Intracellular receptors http://vcell.ndsu.edu/animations/insulinsignaling/index.htm Insulin signalling example

11. Two keys steps for G protein activation/deactiviation: Exchange of GDP for GTP (controlled by guanine exchange factor (GEF) Conversion of GTP to GDP (controlled by GTPase activating proteins (GAPs). This step deactivates adenylyl cyclase and stops production of cAMP.

13. Specific example of kinase activation( cAMP omitted)

15. FAMILYSOME FAMILY MEMBERS ACTION MEDIATED BY FUNCTIONS IGsGs αactivates adenylyl cyclase; activates Ca 2+ channels G G olf αactivates adenylyl cyclase in olfactory sensory neurons IIGiGi αinhibits adenylyl cyclase βγactivates K + channelsK GoGo βγactivates K + channels; inactivates Ca 2+ channelsK α and βγactivates phospholipase C-β G G t (transducin)αactivates cyclic GMP phosphodiesterase in vertebrate rod photoreceptorscyclic GMP IIIGqGq αactivates phospholipase C-β Types of things that g proteins do

16. Another g protein mediated signal pathway : IP3 http://gpcr101.wordpress.com/2011/07/21/camppka-and- ip3dagca2pkc-pathway-animations/ http://bcs.whfreeman.com/lodish5e/content/cat_010/13010- 01.htm?v=chapter&i=13010.01&s=13000&n=00010&o

17. What kinds of cell signals use g proteins? G proteins are important in signal transduction regarding hormone function, taste, smell, and cell growth

18. List of diseases associated with mutations in g proteins: http://themedicalbiochemistrypage.org/signal- transduction.php

19. Action of cholera toxin on g protein mediated receptors