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?

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

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

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

http://www.prism.gatech.edu/~gh19/b1510/signal.htm

http://www.biology.arizona.edu/cell_bio/problem_sets/signaling/overview.html

Good tutorials

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellSignaling.htmlThis one is a bit advanced but lists all known kinds of cell signalling

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_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.htmlG protein mediated work of epimephrine and glycogen very good

http://www.youtube.com/watch?v=iGb93jCKVXs&feature=related

cAMP and kinase example

http://highered.mcgraw-hill.com/olc/dl/120069/bio06.swfIntracellular receptors

http://vcell.ndsu.edu/animations/insulinsignaling/index.htm

Insulin signalling example

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.

Specific example of kinase activation( cAMP omitted)

FAMILY SOME FAMILY MEMBERS

ACTION MEDIATED BY

FUNCTIONS

I Gs α activates adenylyl cyclase; activates Ca2+ channels

Golf α activates adenylyl cyclase in olfactory sensory neurons

II Gi α inhibits adenylyl cyclase

βγ activates K+ channels

Go βγ activates K+ channels; inactivates Ca2+ channels

α and βγ activates phospholipase C-β

Gt (transducin) α activates cyclic GMP phosphodiesterase in vertebrate rod photoreceptors

III Gq α activates phospholipase C-β

Types of things that g proteins do

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

What kinds of cell signals use g proteins?

Second Messenger Examples of Hormones Which Utilize This System

Cyclic AMP Epinephrine and norepinephrine, glucagon, luteinizing hormone, follicle stimulating hormone, thyroid-stimulating hormone, calcitonin, parathyroid hormone, antidiuretic hormone

Protein kinase activity Insulin, growth hormone, prolactin, oxytocin, erythropoietin, several growth factors

Calcium and/or phosphoinositides

Epinephrine and norepinephrine, angiotensin II, antidiuretic hormone, gonadotropin-releasing hormone, thyroid-releasing hormone.

Cyclic GMP Atrial naturetic hormone, nitric oxide

G proteins are important in signal transduction regarding hormone function, taste, smell, and cell growth

List of diseases associated with mutations in g proteins:

http://themedicalbiochemistrypage.org/signal-transduction.php

Action of cholera toxin on g protein mediated receptors