Lecture 1/19 - Signalling Flashcards
Paracrine factors
Type of signalling. Local factors that do not require blood supply
Endocrine hormones
Type of signalling. Must travel in the blood from one organ to another organ
Neurotransmitters
Type of signalling. Travels across a synapse (nerve-to-nerve or nerve-to-muscle)
Autocrine factors
Signals which act on their own tissue
Ligand-gated Ion Channels
A ligand (e.g. acetylcholine) opens the gate to the ion channel (e.g. Na+)
G Protein-Coupled Receptors (GPCR)
Receptors that activate G-proteins by binding GTP. Includes 7TM.
Signal transduction
How we can get a signal to make a response. Between reception and response.
Receptor Tyrosine Kinases
Phosphorylates itself and target proteins
7TM
Similar to bacteriorhodopsin (7 helixes that go back and forth within the membrane) with ligand bound in the middle. Doesn’t pump protons. Mediates many different biological functions. Each thing we smell has its own G-protein receptor. One ligand is epinephrine
second messengers
cAMP, cGMP, and PI3 and diacylglycerol (DAG). When cAMP clipped, forms 5’ AMP which serves to terminate the response of GPCR
Calmodulin
A protein that modulates activities in the presence of calcium
Name the enzyme which reverses the covalent modification
and the consequence of insulin signaling causes in a reversal of the covalent modification that resulted from
epinephrine signaling
Protein phosphatases
Receptor Tyrosine Kinases
a. Dimerize and autophosphorylate when ligand binds
b. FALSE Are used by epinephrine and glucagon
c.
Activate target proteins that may influence cell growth and division
d. FALSE Initiate the transduction leading to fat mobilization
Acetylcholine is a neurotransmitter that
a.
signals a post-synaptic cell by binding to a site on an acetycholine-gated ion channel
embedded in the plasma membrane
b. FALSE triggers Na+ to rush out of the cytoplasm against its concentration gradient
c.
causes a change in voltage measured across the membrane of the post-synaptic cell
d. FALSE excites a post-synaptic neuron by entering its cytoplasm
Epidermal Growth Factor (EGF) and Nerve Growth Factor (NGF)
Upon ligand bonding, the recepter dimerizes and phosphorylates itself. Is a type of RTK
Insulin
Function is to let glucose in after a meal. Receptor type is RTK. It phosphorylates IRSs, which activates a kinase to phosphorylate PIP2 to PIP3, activates PKB. PKB activates Akt. Signalling is terminated by protein phosphatases to remove phosphates from activated proteins in insulin signal transduction pathway
Nuclear Receptor
Transcription factors that contain a hormone binding domain and DNA binding domain. Upon binding to hormone, will go into the nucleus and recognize a specific nucleotide sequence.
G protein
Trimeric protein. Conformational change from the binding of the ligand (e.g. epinephrine) causes a molecule of GDP to unbind and GTP to bind. Causes subunits to disassociate and protein is now activated and activates adenylyl cyclase
Proto-oncogenes
Often RTK genes because they can be converted to an oncogene.
Adenylyl cyclase
A membrane-bound protein that catalyzes the reaction.
H20+ATP->cAMP
The one phosphate that is left, is binding at 1’ and 3’
G protein α subunit
Upon activation, exchanges a GDP for a GTP and disassociates from By dimer and moves in membrane-plane to activate adenylyl cyclase. Also functions as a GTPase that cleaves bound GTP to GDP, causing it to spontaneously reassociate with By dimer and deactivating G protein
IP3 (Inositol triphosphate)
Comes from cleavage of phsophotidylinositol by phospholipase C. May bind to calcium channels in ER, sending calcium into the cytoplasm.
Steroids
Binds to Nuclear Hormone receptors
Ras (Rous avian sarcoma virus)
Ras is active when bound to GTP and inactive when bound to GDP
What binds to steroid hormones?
A nuclear receptor
What alters transcription?
Nuclear receptors, and steroids
What opens Ca++ channels?
IP3 (inostisol triphosphate)
What causes GDP to fall out of when ligand binds to it?
Acetylcholine
What creates cAMP from ATP?
Adenylyl cyclase
What creates GDP from bound GTP?
G protein alpha subunit
What dimerizes an RTK?
Epidermal growth factor (EGF) and Nerve Growth Factor (NGF) and Insulin
What phosphorylates itself?
RTK (Receptor Tyrosine Kinase)
What induces mitosis using Ras?
Epidermal growth factor (EGF) and Nerve Growth Factor (NGF)
What is an example of a paracrine factor?
Epidermal growth factor (EGF) and Nerve Growth Factor (NGF)
What is an example of a hormone?
Insulin, and steroids
What is an example of a neurotransmitter?
Acetylcholine