Signal Transduction

G protein

G protein

The agonist- induced change in conformation of the receptor causes it to bind, activate, and serve as a substrate for a family of specific receptor kinases, called ________- coupled receptor kinases (GRKs)

CGMP

________ is synthesized by receptor guanylyl cyclases and soluble cytoplasmic guanylyl cyclases.

PLCs

________ are cytosolic enzymes that translocate to the plasma membrane upon receptor stimulation.

Endocytosis

________: the plasma membrane folds into the cell and makes a small pocket that encloses the material and eventually pinches off to form a vesicle.

high extracellular concentration

Down- regulation: when the number of receptors decrease due to a(n) ________ of a messenger for some time.

Exocytosis

________: vesicles in the cytoplasm fuse with the plasma membrane and release their contents outside of the cell.

Desmosomes

________: form links between cells, and provide a connection between intermediate filaments of the cell cytoskeletons of adjacent structures- gives strength to tissues.

low extracellular concentration

Up- regulation: when the number of receptors increase due to a(n) ________ of a messenger for some time.

Phagocytosis

________ (cell eating): large particles, such as bacteria and debris from damaged tissues, are engulfed by the plasma membrane.

Β arrestins

________, which have been long associated with receptor desensitization, can also lead to signaling events.

ATPase

________ the catalyzes the breakdown of ATP to ADP.

PKG

________ phosphorylates some of the same substrates as PKA and some that are PKGspecific.

Ions

________: charged, so they can not diffuse across the lipid membrane; have special channels created for them.

Gα

________- the guanine nucleotide- binding subunit; has innate GTPase activity which acts to terminate the signal.

transmembrane protein

It uses a(n) ________ as a carrier.

Substances

________ are said to move downhill.

monomers

Can exist as ________, homodimers, or heterodimers.

ATP

Competitively inhibits ________ binding at the active site of the kinase.

GPCR ligands

________ are classified based on their efficacies for activation of G- proteins.

PI3K

________: increase the level of PIP3 and PKB (also known as Akt)

Steroid sex

Type I: ________ hormones receptors for androgen, estrogen, and.

CAMP

________ and phosphoinositide second messengers act together to stimulate glucose release.

Mitogen

________- activated protein kinases.

IP3

________- mediated mobilization of Ca2+ causes contraction.

G Proteins

________ have 3 subunits.

Heterologous desensitization

________: Second messenger- dependent protein kinases not only phosphorylate agonist- activated GPCRs, but also indiscriminately phosphorylate receptors that have not been exposed to agonist.

medium

The ________ also plays a role: molecules diffuse more rapidly in air than in water.

concentration gradient

For a given ________, the net flux is affected by several factors.

conformational change

They require a(n) ________ to transport the ligand.

Carvedilol

________- antagonist for beta- 1 and beta- 2 adrenergic receptors, so the drug is going to block both these receptor subtypes on cardiac tissue.

particular shape

The first messenger binding site has a(n) ________ into which only certain molecules fit.

RTKs

________ have a wide range of ligands.

GPCRs

________ are classified into six classes based on sequence homology and functional similarities:

Water

________ is polar, but lipids are nonpolar and that is why ________ and lipids do not mix.

K+ pumps

If Na+ /________ are on the basal membrane, this moves Na+ out of the cell into the blood by active transport and Na+ from the lumen into the cell by facilitated diffusion.

Cell membrane

receives and transmits signal

Nucleus

DNA and RNA production

Membrane fluidity

Since there are no chemical bonds between the fatty acid chains, a lot of lateral movement within the membrane is possible

Integral membrane proteins

closely associated with the membrane lipids and are amphipathic proteins

Peripheral membrane proteins

located at the inner or outer membrane surface; do not interact with phospholipid tails

Tight junctions

block the flow of fluids between epithelial cells

Interactions between proteins and ligands

binding

Affinity

strength of logan-protein binding

Chemical specificity

selectivity for one or more ligands

Covalent modulation

covalent bonding of a charged chemical group by an enzyme to a protein that produces a conformational change to the shape of the protein

Allosteric modulation

a protein contains 2 or more binding sites and the noncovalent binding of a ligand to one site can alter the shape and the characteristics (usually the affinity for a ligand) of the other site

Antagonist

A molecule that binds to a receptor but does not elicit a response

Acclimation

number of receptors in the cell membrane can fluctuate

Down-regulation

when the number of receptors decrease due to a high extracellular concentration of a messenger for some time

Up-regulation

when the number of receptors increase due to a low extracellular concentration of a messenger for some time

Flux

amount of material crossing a surface unit (cm2) per time unit (s)

Ions

charged, so they cannot diffuse across the lipid membrane; have special channels created for them

Endocytosis

the plasma membrane folds into the cell and makes a small pocket that encloses the material and eventually pinches off to form a vesicle

Exocytosis

vesicles in the cytoplasm fuse with the plasma membrane and release their contents outside of the cell

Fluid endocytosis

the endocytotic vesicle simply encloses a small volume of ECF

Phagocytosis (cell eating)

large particles, such as bacteria and debris from damaged tissues, are engulfed by the plasma membrane

Ezetimibe

Inhibits absorption of cholesterol in the small intestine via the sterol

Kinase

enzyme that adds phosphate groups

Receptor Tyrosine Kinases (RTK)

receptors with intrinsic tyrosine kinase activity

Non-receptor Tyrosine Kinase (NRTK)

intracellular proteins that are responsible to phosphorylating a variety of intracellular proteins on tyrosine residues

Type I

Steroid sex hormones receptors for androgen, estrogen, and

Type II

Thyroid hormone, vitamin A & D and retinoid receptors

Class A

Rhodopsin-like receptors

Class C

Metabotropic glutamate receptors

Class D

Fungal mating pheromone receptors

Class E

Cyclic AMP receptors

Class F

Frizzled and Smoothened receptors

M1, M3, M5 receptors

Gq

M2 and M4 receptors

Gi

D1-like receptors (D1 and D5)

Gs

H2

Gs

H3

Gi

Receptor Regulation

what if there is a constant presence of ligand/agonist

Homologous desensitization

Specific G protein-coupled receptor kinases (GRKs) selectively phosphorylate agonist-activated receptors

Heterologous desensitization

Second messenger-dependent protein kinases not only phosphorylate agonist-activated GPCRs, but also indiscriminately phosphorylate receptors that have not been exposed to agonist

Example

Intestinal mucosa and vascular smooth muscle

Liver

complementary phenomenon

Full agonists, partial agonists, antagonists, or inverse agonists

depending on their abilities to elicit a receptor-mediated response

Carvedilol

antagonist for beta-1 and beta-2 adrenergic receptors, so the drug is going to block both these receptor subtypes on cardiac tissue

fluid mosaic

model that acknowledges the lateral movement within a cell membrane and accounts for the proteins in the phospholipid bilayer

integral membrane protein

protein category that includes all amphipathic proteins; associated with membrane lipids; includes transmembrane proteins

peripheral membrane protein

protein category that does not span the membrane; inner side is associated with cell shape and motility

tight junction

cellular connection that blocks the flow of fluids between epithelial cells

desmosome

cellular connection that forms links between the intermediate filaments of cell's cytoskeletons; gives strength to tissues

gap junction

cellular connection that forms pores between connecting adjacent cells

golgi

newly synthesized polar membrane proteins get to the surface/outside of the cell by being packaged into vesicles by which organelle?

ligand

any molecule bound to a protein

affinity

strength of ligand-protein binding

chemical specificity

selectivity for one or more ligands

covalent modulation

covalent bonding of a charged chemical group by an enzyme to a protein that produces a conformational change to a protein

allosteric modulation

when a protein contains two or more binding sites and non-covalent binding of a ligand to one site can alter the shape/characteristics of another site

second messenger

response is relayed by another chemical messenger inside the cell

first messenger

response is relayed by the original chemical messenger

structurally similar

certain molecules can elicit weaker responses on a receptor if they are __________ to the endogenous ligand

saturation

degree to which receptors on a cell are occupied by a messenger

agonist

chemical messenger that binds to a receptor and triggers the normal response

antagonist

molecule that binds to a receptor but does not elicit a response

flux

amount of material crossing a surface unit per time unit

diffusion equilibrium

net flux = zero

diffusion

movement of a substance from high concentration of a substance to lower concentration; no energy required