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80 Cards in this Set
- Front
- Back
Why do cells need to respond to signals?
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Need to respond to a changing environment: Adaptation or a cellular response is critical for survival.
Cells need to communicate with each other. To Modify cellular metabolism, function, movement To modify gene expression, development |
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How does glucose act as a signal to yeast cells
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Glucose acts as a signal to yeast cells to increase number of glucose transporters and enzymes allowing efficient uptake and use of glucose
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What is Auxin
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a signaling molecule transmitted from cell to cell and inhibited by the light
(darwin and son investigated phototropism, cell-to-cell communication mediated by Auxin) |
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What are the features of signal transducing systems?
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Specificity
Amplification Desensitization/Adaptation Integration |
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define Specificity within a signal transducing system
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Signal molecule fits binding site on its complementary receptor, other signals do not fit.
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Define Amplification in terms of signal transducing systems
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When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade.
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Define Desensitization/Adaption in terms of signal transducing systems
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Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface.
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Define Integration in terms of signal transducing systems
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When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger X, or the membrane potential Vm the regulatory outcome results from the integrated input from both of the receptors.
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What are the five types of signals relayed between cells
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Direct intercellular signaling
Contact-dependent signaling Autocrine signaling Paracrine signaling Endocrine signaling |
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Define Direct intercellular signaling
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Cell junctions allow signaling molecules to pass from one cell to another
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Define Contact-dependent signaling
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Some molecules are bound to the surface of cells and serve as signals to cell coming in contact with them.
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Define Autocrine signaling
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Cells secrete signaling molecules that bind to their own cell surface or neighboring cells of the same type.
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Define Paracrine signaling
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Signal does not affect cell secreting the signal but does influence cells in close proximity (synaptic signaling)
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Define Endocrine signaling
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Signals (hormones) travel long distances and are usually longer lasting
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What are three stages of cell signaling
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1. Receptor activation when signaling molecule binds to receptor.
2. Signal transduction when the activated receptor stimulates sequence of changes -- signal transduction pathway 3. Cellular response including the alteration of activity of one or more enzymes, the altered structural protein function, the change of gene expression. |
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What is the cellular response to the alteration of activity of 1 or more enzymes
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Altered metabolism or other cell functions
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What is the cellular response to the alteration of structural protein function
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Altered cell shape or movement
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What is the cellular responce to a change in gene expression
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Altered gene expression changes the amounts of proteins in the cell
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What is a Ligand?
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a signaling molecule that rapidly binds noncovalently to a receptor with a high degree of specificity.
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What effects do ligands have on receptors and what is a hormon receptor complex?
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Ligands alter receptor structure - a conformational change.
Hormone-receptor complexes are activated receptors that can initiate cellular responses |
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What are enzyme linked receptors
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cell surface receptors found in all living species, the Extracellular domain binds signal (hormon/ligand) causes intracellular domain to become a functional catalyst.
an example are protein kinases |
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what is Kd
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Kd is a measure of the affinity of a ligand for its receptor (molecular complementarity -- specificity). The concentration of ligand at half its receptors occupied, Kd, is experimentally determined.
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What are agonists
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Agonists are structural analogs that bind to a receptor and mimic the effects of its natural ligand.
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what are antagonists
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Antagonists are analogs that bind the receptor without triggering the normal effect and thereby block the effects of agonists.
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is it necessary for most receptors to be occupied by a ligand to have a max physiological response?
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no, the max physiological response occurs when only a fraction of receptors are occupied by a ligand. Well before Kd for ligand binding is reached.
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What determines the sensitivity of a cell to external signals?
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the number of surface receptors and their affinity for ligand.
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What is transduction?
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Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
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What are the benifit of signal transduction involving multiple teps?
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multistep pathways can amplify a signal: a few moleculs can produce a large cellular response
multistep pathways provide more opportunities for coordination and regulation of the cellular response. |
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in signal transduction pathways, what molecules generally relay a signal from receptor to response?
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mostly proteins
the receptor activates another protein, which activates another and so on until the protein producing the response is activated (cascade) at each step, the signal is transduced into a different form, usually a shape change in a protein |
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what are six types of signal transducers?
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G protein-coupled receptor
Receptor tyrosine kinase Receptor guanylyl cyclase Adhesion receptor (integrin) Gated Ion Channel Nuclear receptor |
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What si a G protein-coupled receptor
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External ligand binding to receptor, activates an intracellular GTP-binding protein which regulates an enzyme that generates an intracellular second messenger.
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What is receptor tyrosine kinase?
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Ligand binding activates tyrosine kinase activity by autophosphorylation
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What is Receptor guanylyl cyclase
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ligand binding to extracellular domain stimulates formation of second messenger cyclic GMP
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What is Adhesion receptor (integrin)
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Binds molecules in extracellular matrix, changes conformation, thus altering its interaction with cytoskeleton
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What is a gated ion channel
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opens or closes in response to concentration of signal ligand or membrane potential.
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What is a nuclear receptor
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Steroid binding allows the receptor to regulate the expression of specific genes.
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some facts about G-protein coupled receptors (GPCR)
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common in eukaryotes
protein contains 7 transmembrane segments Activated receptor binds to G protein Releases GDP and binds GTP instead GTP causes G protein to disassociate Subunit and b/g dimer interact with other proteins in a signaling pathway |
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What is the role of Guanine exchange factor?
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They function as activators of small GTPases. GEFs activate G proteins by promoting this nucleotide exchange
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In many pathways, the signal is transmitted by a cascade of ____________.
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protein phosphorylations
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what do protein kinases do?
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protein dinases transfer phosphates from ATP to protein, a process called phosphorylation
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What do protein phosphatases do?
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protein phosphatases remove the phosphates from proteins, dephosphorylation
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what acts as a molecular switch, turning activities on and off?
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phosphorylation and dephosphorylation systems
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What is a pathways first messenger?
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the extracellular signal molecule that binds to the receptor is a pathways first messenger
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What is a signal pathway's second messenger?
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second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
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what pathways do second messengers participate in?
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second messengers participate in pathways initiated by G protein coupled receptors and receptor tyrosine kinases
cAMP Ca2+ Diacylglycerol and inositol triphosphate |
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what are
cAMP Ca2+ Diacylglycerol and inositol triphospate examples of? |
second messengers
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what does cAMP stand for
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Cyclic adenosine monophosphate
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what is the signal transduction via cAMP?
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its the signal binding to GPCR activating G protein to bind GTP causing dissociation.
One type of subunit binds to adenylyl cyclase stimulating synthesis of cAMP One effect of cAMP is to activate protein kinase A (PKA) Activated catalytic PKA subunits phosphorylates specific cellular proteins When signaling molecules are no longer produced, eventually effects of PKA are reversed |
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what are the two advantages of cAMP
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signal amplification -- binding of signal to single receptor can cause the sythesis of many cAMP that activate PKA, each PKA can phosphyrlate many proteins
Speed -- in one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal |
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All about signal transduction via Ca2+
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Cells maintain a large Ca2+ gradient
2 types of calcium pumps When calcium channels open, an influx of Ca2+ acts as a second messenger |
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What are some examples of signal transduction via Ca2+ in plants and animals?
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Plants: phototropism, opening and closing of stomata, gravitropism
Animals- nerve transmission, muscle contraction, secretion of digestive enzymes |
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where are high concentrations of Ca2+ found in the cell?
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the Extracellular fluid, ER Lumen, and mitochondrial Matrix.
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All about Signal transduction via diacylglycerol and inositol triphosphate
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Second way for an activated G protein to influence signal transduction pathways
A subunit can activate phospholipase C Diacylglycerol (DAG) and inositol triphosphate(IP) are made from plasma membrane phospholipid Ca2+ channels in ER open Variety of effect of Ca2+ on cell behavior see diagram... |
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what is the general structure of G protein coupled receptors?
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All G protein–coupled receptors (GPCRs) contain seven membrane-spanning regions with their N-terminal segment (NH3+) on the exoplasmic face and their C-terminal segment (COO-) on the cytosolic face of the plasma membrane
All receptors of this type contain seven transmembrane α-helical regions. The loop between α helices 5 and 6, and in some cases the loop between helices 3 and 4, which face the cytosol, are important for interactions with the coupled G protein. |
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What hormone signals the need to fight or flee?
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Epinephrine
Epinephrine, which binds to two types of GPCRs, is particularly important in mediating the body’s response to stress, such as fright or heavy exercise, when all tissues have an increased need for glucose and fatty acids. These principal metabolic fuels can be supplied to the blood in seconds by the rapid breakdown of glycogen in the liver (glycogen-olysis) and of triacylglycerol in the adipose storage cells (lipolysis). |
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When does Epinephirne action begin?
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When the hormone binds to Adrenergic receptors which of are of four general types α1, α2, β1, and β2, defined by differences in their affinities and responses to a group of agonists and antagonists
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Where are β-adrenergic receptors found and what responses to epinephrine does it mediate
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β-adrenergic receptors on muscle, liver, andadipose tissue. These receptors mediatechanges in fuel metabolism, including theincreased breakdown of glycogen and fat.
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Where are α-adrenergic receptors found and what responses to epinephrine does it mediate
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α-adrenergic receptors on smooth muscle cells in kidneys, GI etc. Binding to thesereceptors causes arteries to constrict
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how is the long C3 loop critical to interaction with G protein?
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The C3 loop determins the specificity of G protein binding when compaired to alpha 2 Adrenergic receptor and beta 2
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for the effector Adenylyl cyclase, what is the second messenger, Gα class, and the Receptor example?
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cAMP (increased), Gαs, and β-adrenergic (epinephrine) receptors: receptors for glucagon, serotonin, vasopressin
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for the effector Adenylyl cyclase K+ channel (Gbetay activates effector), what is the second messenger, Gα class, and the Receptor example?
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cAMP (decreased) Change in membrane potential, Gαi, α2-Adrenergic receptor Muscarinic acetylcholine receptor
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for the Gα class Gαolf, what is the associated effector, what is the second messenger, and the Receptor example?
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Adenylyl cyclase, cAMP (increased) Oderant receptors in nose.
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for the Gα class Gαq, what is the associated effector, what is the second messenger, and the Receptor example?
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Phospholipase C, IP3'DAG(increased), α1-Adrenergic receptor
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for the Gα class Gαo, what is the associated effector, what is the second messenger, and the Receptor example?
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Phospholipase C, IP3'DAG (increased), Acetylcholine receptor in endothelial cells
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for the Gα class Gαt, what is the associated effector, what is the second messenger, and the Receptor example?
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cGMP phosphodiesterase, cGMP (decreased), Rhodopsin (light receptor) in rod cells
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Ligand-Gated Ion channels: three random facts
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found in plant and animal cells
Ligand binding causes ion channels to open and ions to flow through the membrane Animals- signals between nerve and muscle cells, between 2 nerve cells, Ca2+ uptake |
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what kind of receptors in the heart muscle activate G proteins that open K channels
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Muscarinic Acetylcholine receptors in the heart muscle activate G proteins that open K channels. Hyperpolarization reduces frequency of cardiac muscle contraction
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Epinephrine, Glucagon, ACTH are examples of ___________ that ________________
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stimulatory hormones that activate Adenylyl Cylase
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PGE1 and Adenosine are examples of ___________ that _______________
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Inhibitory hormones that inhibit Adenylyl Cylase
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how does cAMP activate PKA?
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by releasing Cat subunits. Regulatory subunits have pseudosubstrate seq which keeps cat subunits inactive
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Intracellular receptor proteins are found in the cytosol or nucleus of target cells, what kind of chemical messengers can activate receptors?
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small or hydrophobic chimical messengers can readily cross the membrane and activate receptors
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what are two examples of hydrophobic messengers?
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steroid and thyroid hormones of animals
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An activated hormone-receptor complex can act as a _______________, turning on specific genes
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transcription factor
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How does Estrogen act with an intracellular receptor?
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estrogen passes through membrane and binds to receptor in nucleus
Dimer of estrogen-receptor complexes binds to DNA to activate transcription of specific genes. |
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How does Auxin act as an intracellular receptor
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Binding of auxin in the cytosol activates TIR1
Gene regulation is not direct, but causes breakdown of inhibitory proteins, with gene inhibition relieved, genes are transcribed. |
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What three classes of organisms have a two component regulatory system -- cellular response?
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Bacteria, fungi, and plants. (not animals)
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What are the two components of the two component regulatory system found in bacteria fungi and plants
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Sensor Kinase, an Enzyme linked receptor that hydrolyzes ATP and phosphorylates- phosphate group transferred to response regulator
Response Regulator: regulates expression of many genes |
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What is NarQ/NarL?
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A two component regulatory system
Senses presence of nitrate (NO3- and nitrite (NO2-) Binding phosphorylates NarQ Transfers phosphate to NarL (response regulator) Activates genes involved in nitrate/nitrite metabolism and transport |
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Insulin and the Insulin receptor result in a
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hormon induced dimerization leading to a Cross phosphorylation, and an Activated JAK2 (receptor) Which follows an enzymatic reaction and amplification. The phophorylated IRS proteins follow protein protein interaction resulting in localized phosphoinositide 3 kinase. This enzymateic reaction is amplified resulting in phosphotidylinositol-3-4-5-triphospate (PIP3) which goes through a protein-lipid interaction leading to an Activated PIP3-dependent protein kinase - another enzymatic reaction and amplification results in an Activated AKt protein kinase eventually increasing the glucose transporter on cell surface
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Signal integration, four possibilities
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Pathway leads to a single responce
Pathway branches leading to two responses Cross-talk occurs between two pathways, resulting in one response Different receptor (same signaling molecule) leads to a different response. |