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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