Patho Exam 2: Signals part 2

What type of G protein is activated by a-adrenergic receptors?

Gaq

What enzyme does Gaq activate when in GTP form?

Phospholipase C

where are a-adrenergic receptors expressed

in muscle cells that control pupil dilation and line small blood vessels in the skin

do a/b adrenergic receptors have the same signal

yes, epinephrine

phospholipase C

cleaves PIP2 into IP3 and DAG (2nd messengers)

IP3

soluble second messenger that diffuses away from the membrane

what does IP3 cause

rapid release of Ca from the ER through specific IP3 gated Ca2+ channel proteins

Ca is also a signaling molecule and

second messenger

DAG is a second messenger that

remains in the plasma membrane

What does DAG bind to and activate?

protein kinase C (PKC)

PKC requires _____ to bind to DAG

Ca

how do you activate protein kinase C in the phosphoinositide cascade

Ca and DAG have to bind to PKC to have the most amplification

Calmodulin

a common Ca sensor

calcium can bind to it

Ca binding to calmodulin induces

conformational changes

the conformational changes of calmodulin cause

hydrophobic surfaces to be exposed and therefore bind to proteins such as kinases

caffeine is a

adenosine receptor antagonist

Insulin

hormone released in response to inc blood glucose levels after a meal

how is insulin receptor inhibited

auto inhibited by binding to itself

the insulin receptor is

a protein tyrosine kinase

the insulin receptor is a homodimer of

heterodimers

where do the a chains, b chains, and tyrosine kinase domain of the insulin receptor lie

a chains are outside of the cell

B chains are inside the cell

tyrosine kinase is inside of the cell

insulin binding results in the _______ _______ and ___________ of the insulin receptor

cross phosphorylation and activation

conformational change of the insulin receptor brings

protein kinase domains together

what leads to the activation of the insulin receptor kinase

cross phosphorylation of tyrosine residues

the flexible loops of one tyrosine kinase subunit fits into the active sit of

the other tryrosine kinase active site (cross phophorylation)

the cross phosphorylation causes the activation loop to swing out which opens the active and

activate the kinase

what will the activated kinase do

phosphorylate IRS proteins and membrane-associated anchor proteins

phosphoinositide 3 kinases (PI3Ks)

add a phosphoryl group to PIP2 forming PIP3

what do PIP3 molecules serve as

gathering points for other proteins to continue the kinase cascade

what is the net effect of insulin binding

increased glucose uptake

insulin binding to the receptor induces

cross-phosphorylation and activation of IR-Kinase

phosphorylated IRS proteins will attract

PIP3

PIP3 activates

PDK1 kinases

increase in glucose transporters on cell surfaces promotes

glucose uptake, utilization, and storage in those cells

how is insulin signaling terminated

phosphatases

Protein Tyrosine Phosphatases

remove phosphate groups from tyr residues on the insulin receptor

protein serine phosphateses

remove phosphates from activated protein kinases such as PKB

Lipid phosphatases

remove phophates from inositol lipids such as PIP3

Epidermal Growth Factor (EGF)

signaling polypeptide that stimulates the growth of epidermal and epithelial cells

where is EGF released into

regions where wounding occurs

EGF receptors

monomeric receptor tyrosine kinases that bind a single molecule of EGF in its extracellular domain

EGF binding to the EGF receptor induces

receptor dimerization

binding of EGF to EGF receptor results in the activation of

Ras

EGF receptor dimerization results in ________ phosphorylation and downstream activation of _____

EGFR, Ras

what is Ras

a small G protein that exchanges GDP for GTP and undergoes a conformational change

what type of molecule is EGF

signaling

what is the net effect of EGF binding to EGFR

gene expression changes and promote growth/wound healing

how do protein phosphatases terminate EGF signaling

protein phosphatase remove phosphoryl from Tyr residues on EGF receptors and Ser, Thr, Tyr residues in protein kinases

how does Ras terminate EGF signaling

intrinstic GTPase activity

how do GAP proteins terminate EGF signaling

facilitate GTP hydrolysis

genes encoding Ras proteins are commonly mutated in

human tumors

most common Ras mutations lead to

a loss of the ability to hydrolyze GTP trapping Ras in the on position

what receptor family is over expressed in many cancers

EGFR

sensory systems are based on

specialized signal-transduction pathways

most odorants are small ______ organic compounds

volatile

what determines the perception of odors

the shape of the molecule determines what receptors they bind to

the olfactory signal transduction cascade is similar to what

B adrenergic receptor

odorant binding to an OR on the

neuronal surface

what the odorant binds to the OR what does it initiates

signal transduction cascade that results in an action potential

the rise of cAMP in olfactory activates what

nonspecific cation channel

vision is based on the absorption of visible light by

photoreceptor cells in the eye

vision relies on what receptor to signal response to absorbed light

specialized 7TM receptor

rhodopsin

photoreceptor that absorbs light efficiently in the middle of the visible spectrum

what does rhodopsin consist of

the protein opsin combined with retinal (a prosthetic group) via a lysine residue

light absorption results in the isomerization of the 11-cis-retinal group of rhodopsin to

all trans form

transducin

heterotrimeric G protein

transducin activates

cGMP phosphodiesterase

cGMP phosphodiesterase hydrolyzes

cGMP to GMP causing cGMP-gated ion channel to close