Cell to cell communication = Cell signalling
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?
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)
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
Good tutorials
http://www.prism.gatech.edu/~gh19/b1510/si
gnal.htm
http://www.biology.arizona.edu/cell_bio/probl
em_sets/signaling/overview.html
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
http://highered.mcgrawhill.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
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)
Types of things that g proteins do
FAMILY
SOME FAMILY
MEMBERS
I
Gs
α
activates adenylyl
cyclase; activates
2+
Ca channels
Golf
α
activates adenylyl
cyclase in olfactory
sensory neurons
Gi
α
inhibits adenylyl
cyclase
βγ
activates K
channels
βγ
activates K
channels;
2+
inactivates Ca
channels
II
Go
III
ACTION MEDIATED FUNCTIONS
BY
+
+
α and βγ
activates
phospholipase C-β
Gt (transducin)
α
activates cyclic
GMP
phosphodiesterase
in vertebrate rod
photoreceptors
Gq
α
activates
phospholipase C-β
Another g protein mediated signal pathway : IP3
http://gpcr101.wordpress.com/2011/07/21/camppka-andip3dagca2pkc-pathway-animations/
http://bcs.whfreeman.com/lodish5e/content/cat_010/1301001.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
Cyclic GMP
Epinephrine and norepinephrine, angiotensin II, antidiuretic
hormone, gonadotropin-releasing hormone, thyroid-releasing
hormone.
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/signaltransduction.php
Action of cholera toxin on g protein mediated
receptors