lecture 17 signal transduction Flashcards
pathway
signal -> receptor -> transduction -> response
categories of signals
endocrine, paracrine, neurotransmitters
endocrine factors
hormones that travel throughout bloodstream to a distant organ
paracrine factors
released from one organ to a nearby organ. or itself if autocrine
neurotransmitters
released across synapses (gap between neurons)
what’s special about acetyl choline and what it does?
same signal causes different reactions in different cells. acetyle choline in heart decreases contractions, in salivary gland causes secretion, in skeletal muscle causes muscle contractions
classes of receptors
nuclear hormones, ligand gated ion channels, G-protein receptors, enzyme-linked receptors
nuclear hormone receptors
receptors for steroid hormones
ligand gated
nerves communicating w/ nerves and muscles
G-protein coupled receptors
traverse the membrane with 7 alpha helices. Bind GDP/GTP
enzyme-linked receptors
membrane proteins that dimerize then recruit protein kinases, OR dimerize and then become protein kinases
T/F: Transduction mechanisms differ for each class of receptor
true
what happens with hydrophobic vs hydrophilic signals?
hydrophobic signals diffuse across the cell membrane, while hydrophilic signals do not enter the cell, and receptors are on the surface
what’s the mechanism going on for hormone receptors?
steroid hormones diffuse across membrane. hydrophobic. receptor waits for them in either the cytoplasm or the nucleus, recognizes a target sequence on their DNA, and changes transcription of genes accordingly
what are the two domains that the nuclear hormone receptors have?
hormone binding domain and DNA binding domain.
what happens that activates the intracellular receptor protein for nuclear receptors?
the signal binds and causes a conformational change. this brings the whole molecule (activated receptor) to the nucleus where it can find its target gene
ligand gated channels
binding of a ligand such as acetylcholine opens the channel to allow the facilitated diffusion of a specific ion. ex: acetylcholine opens sodium channel in muscle cells
G-protein coupled receptors
signal binds as a ligand in the 7-alpha helices. binding causes G protein to change conformation, dumping out a GDP and dissociating from beta and gamma unit, taking up a GTP. then, activated receptor can trigger adenylate cyclase, trigger cyclic AMP, etc
cyclic AMP is what kind of molecule?
allosteric effector molecule . activator of protein kinase
how do G-proteins shut themselves off ?
through hydrolysis of GTP, or through epinephrine concentration just falling off
enzyme-linked receptors
phosphorylates stuff. either itself or a target protein to activate them. tyrosoine kinase receptor is already a kinase itself, while growth hormone receptor acts on behalf of RTK to phosphorylate stuff
how do enzyme linked receptors actually work , in terms of the activation?
ligands dimerize the receptor, which enables it to bind to and activate other kinases
how does EGF receptor work?
The binding of epidermal growth factor (EGF) to its receptor leads to cross-phosphorylation of the receptor. The phosphorylated receptor binds Grb-2, which, in turn, binds Sos. Sos stimulates the exchange of GTP for GDP in Ras. Activated Ras binds to protein kinases and stimulates them
What is ras?
Ras activates kinases that affect growth and cell division
Growth Factor receptors (GF-RTKs)
Growth Factor receptors (GF-RTKs) autophosphorylate and may recruit proteins that activate Ras-GDP by removing the GDP so GTP binds.
Transduction Mechanisms
A. voltage change (electrical potential change) leads to neuronal signaling and muscle contraction.
B. Increasing concentration of “second messengers” that act to alter target protein shape when bound
C. Activate or inhibit transcription such as steroid binding to nuclear receptors. Hormone-receptor complex binds promoters on DNA
D. Activation of kinases that phosphorylate other proteins or enzymes to activate or inhibit them
how does increasing the concentration of second messengers act as a transduction mechanism?
alters target protein shape when bound
name the 2 ways that 7TM does transduction
1) activates adenylyl cyclases which creates cAMP from ATP. cAMP is an allosteric activator of protein kinase A
2) releases IP3 which opens a calcium ion channel and activates proteins such as calmodulin
name some commonly used second messengers
cAMP, calcium ion, IP3, DAG
why do we care about calcium ion? what does it do that is special?
Ca2+ is an important second messenger in eukaryotic signal transduction pathways. It triggers exocytosis of secretory vesicles in neurons and actin-myosin interaction in muscle contraction. It also binds calmodulin, a common Ca2+ sensor.
The Ca2+-calmodulin complex activates a variety of biochemical targets, including pumps, such as the plasma membrane Ca2+ ATPase, and the calmodulin-dependent protein kinase (CaM kinase).
what kind of receptor would already contain a tyrosine kinase domain in their covalent structure
receptor tyrosine kinases (RTK)
___was the first known case of a virus causing cancer (oncogenic virus).
Ras (Rous avian sarcoma virus)
how does steroidal binding to nuclear receptors transduction mechanism work?
After diffusing across the bilayer, the hormone binds noncovalently to its receptor waiting in the cytoplasm (or in the nucleus). The hormone-receptor complex finds specific target genes in the DNA and activates transcription of a specific gene (e.g., estrogen activates ovalbumin gene to make this protein for chick egg whites
how does the kinase transduction mechanism work with growth factors?
Growth Factor receptors (GF-RTKs) autophosphorylate and may recruit proteins that activate Ras-GDP by removing the GDP so GTP binds. Ras activates kinases that affect growth and cell division.
how does the kinase transduction mechanism work with receptor tyrosine kinases? ex: insulin
The polypeptide hormone insulin is secreted when the blood is rich in glucose. Receptor dimers form on insulin binding, leading to cross-phosphorylation and activation of the kinase domains. The activated kinase of the insulin receptor phosphorylates insulin-receptor substrates…
to creates PIP3. PIP3 activates Protein Kinase B (PBK) which activates glycogen synthesis enzymes and increases glucose transporters on the plasma membrane
termination of transduction pathway; phosphate reason
Phosphatases remove the activating phosphates from target proteins, cAMP is clipped by phosphodiesterase to form AMP
terminatin of transduction response pathway; GTP
G protein response is self-limiting because alpha subunit that holds the GTP is also a slowly acting GTPase.
