all have similar seven pass transmembrane structure.
all interact with guanine nucleotide binding G-proteins.
Activation of G proteins
Ligand binding activates receptor.
Receptor triggers affinity change for GDP and GTP.
Two major parts of G-protein become active.
Each G-protein subunit mediates signaling.
G protein signaling
both alpha and beta gamma subunit interact with membrane proteins by binding.
G-protein binding regulates the activity of the target protein- up or down.
How G-proteins inactivate
Alpha subunit has GTPase activity.
GTP hydrolysis turns alpha subunit off.
Reassembly of the G-protein turns of the gamma delta subunit.
What are the targets of Gproteins
More Gproteins than Gprotein associated receptors.
at least 20 different G-protein heterodimers are known, most activated by separate receptors.
Major G-protein Targets
Plasma membrane ion channels
enzymes which produce second messengers.
Most common G-protein second messengers
Cyclic AMP- via activation of adenyl cyclase.
diacylglycerol(DAG) and inositol triphosphate(IP3)
Activation of Second Messengers
activated by adenyl cyclase generates cAMP.
this commonly leads to activation of protein kinases A.
what does cAMP do for protein kinases A
PKA then go on to activate additional signals.
cAMP signaling cascades lead to cellular responses.
How are protein kinases regulated
Phosphorylation- by other kinases or self.
Allosterism- cAMP, CGMP, Ca
Location- transport to or isolation from their substrate proteins.
Lots of kinases
about 2% of 30,000 human genes code for kinases.
average mammalian cell contains 100s of distinct protein kinases.
animal protein kinases phosphorylate three amino acids
How are plants different with kinases?
They don't use protein tyrosine kinases.
They do use histidine kinases.
they don't use cyclic-AMP signaling cascades (no PKA)
They don't use steroid nuclear receptors.
Enzyme Linked receptors: cell surface. What are the major subtypes in animals?
receptor kinases- tyrosine kinases, and receptor serine/threonine kinases.
indirect kinase receptors- activated bind to kinases and activate them.
Receptor tyrosine kinases
upon binding ligand receptors dimerize and auto-phosphorylation occurs.
phosphate binding "adaptor" trigger signal transduction.
Indirect Tyrosine kinase receptors
Dimerized receptors bind JAK proteins.
Activation of JAK leads to phosphorylation of receptors.
modified receptors bind to STAT proteins.
Why is signaling cross-talk and integration important?
multiple signals can regulate one signaling cascade which is important for intregration of information. which is important for weak signals that are important to be heeded, and strong but less important signals to be ignored.
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