Powerpoint 4 Chapter 14 Flashcards
epinephrine receptor
beta-andrenergic
epinephrine causes
energy-store mobilization
insulin causes
increased glucose uptake
EGF causes
expression of growth-promoting genes
signal transduction steps
1) release of primary messenger 2) reception of primary messenger 3) transduction. receptor releases second messengers 4) Activation of effectors 5) termination
effector
controls channels or pumps, enzymes, or proteins that control gene expression
common second messengers
cAMP, Ca++, inositol, DAG
three receptor types of signalling pathways
G-protein coupled, enzyme linked, ligand gated ion channels
enzyme linked receptors have ? or ? activity
cytoplasmic tyrosine kinase, guanylyl cyclase
G-protein receptors AKA
7-transmembrane helix receptors
7TM receptors only found in ?
eukaryotes
first member of the 7TM family discovered
Rhodopsin
?% of therapeutic drugs target 7TM receptors
50
bind to andrenergic receptors to activate
agonists
inhibit actvation
antagonists
types of andrenergic receptors
alpha 1 and 2, beta 1,2 and 3
consequence of ligand binding to 7TM
conformational change converts receptor into a guanine nucleotide exchange factor. activation of G protein trimer (of alpha, beta, and gamma subunits) because the alpha subunit binds guanyl nucleotides causes the alpha subunit to dissociate.
activation of adenylate cyclase by alpha subunit of G-protein causes
conversion of ATP into cAMP
beta-andrenergic receptor is a type of ?
7TM receptor
epinephrine binding to beta-andrenergic receptor resulting pathway
activation, conformatinal change. activation of G-protein and dissociation of alpha subunit. protein interaction with adenylate cyclase activates. enzymatic reaction to form cAMP. activated protein kinase A.
pathway linking activated Protein Kinase A to mobilization of stored CHO
PKA activates phosphoryl kinase. phosphoryl kinase activates phosphorylase. phosphorylase initiates synthesis of glucose from glycogen.
four ways of regulating signaling
at the receptor (agonist/antagonist, desensitization), the g-protein itself, second messenger, protein kinases
receptors turned of by?
dissociation of signal molecule
receptors desensitized by?
phosphorylation of cytoplasmic C-terminal and binding of b-arrestin
G-proteins are timers because..
they turn off by hydrolyzing GTP to GDP and Pi
cAMP is degraded by
soluble phosphodiesterase
ACE inhibitors are important for?
lowering blood pressure
ACE stands for
angiotensin converting enzyme
angiotensin is produced by ACE and causes
vasoconstriction by activating a G-protein that activates Phospholipase C
signaling via phospholipase C releases these two secondary messengers from cleavage of PIP2
IP3, DAG
Protein kinase C can be artificially activated by addition of ?
phorbol esters that bind to DAG site and a calcium ionophore
IP3 causes
rapid release of Ca++
PKC ordinarily activated by ?
DAG
fertilization of an egg causes a wave of ? in the cytoplasm. It can be monitored by fluorescence.
Ca++
common Ca++ binding site
EF Hand motif
two important Ca++ binding proteins
calmodulin and annexins
calmodulin activation causes
exposing of hydrophobic patches that bind target proteins. ex. activation of CaM kinase
CaM kinase function
phosphorylates target proteins that regulate metabolism, ion permeability, and neurotransmitter release
common signals of enzyme linked receptors
insulin, EGF
insulin receptor structure
dimer of alpha-beta subunits. insulin binding site is between the two alpha subunits outside of cell
result of insulin binding to insulin receptor
autophosphorylation followed by phosphorylation of target proteins such as insulin receptor substrates
the insulin receptor is a ? kinase
tyrosine
the insulin receptor substrates share (3)
pleckstrin domain, SH2 domains, four Tyr phosphorylation sites
pleckstrin domain function
binds PIP2
SH2 domain function
binds phosphotyrosine
Akt-2, activated by insulin receptor phosphorylation cascade, is a protein kinase that ?
stimulates fusion of GLUT4 receptor vesicles to plasma membrane
phosphotyrosine of IRS-1 recruits ?
cytosolic PI3 kinase
? domain of PI3 kinase binds to IRS-1
SH2
binding of PI3 kinase to IRS-1 allows ?
it to interact with its membrane substrate
PI3 kinase produces the secondary messenger ?
PIP3
phosphatases ? and ? convert PIP3 back to PIP2
PTEN and SHIP
insulin signaling pathway
activated receptor. phosphorylated IRS proteins. localized PI3 kinase. production of PIP3. activated PIP3 dependent protein kinase. activated Akt protein kinase. increased glucose transporter on cell surface.
? removes activated receptor
receptor recycling
Akt is dephosphorylated by ?
PHLPP
EGF binding to its monomeric receptor causes
a conformatinal change that leads to dimerization
dimerization of EGF receptor activates ?
autophosphorylation of tyrosines in the c-terminal tail
phosphotyrosine tails of EGF receptor recruit ?
adaptor proteins like Grb-2
SH3 domain of Grb-2 binds to ?
proline-rich portions of the protein SOS
SOS
guanine nucleotide exchange factor protein that activates a small G protein called Ras
Ras initiates ?
phosphorylation cascade by activation of Raf
oncogene
leads to cancerlike characteristics in susceptible cell types
c-Src vs v-Src
c-Src contains key tyrosine residue near its C-terminal that when phosphorylated binds to upsteam SH2 region. v-Src lacks this and can not be turned off and leads to unregulated cell growth.
? mutations are the most common mutations in tumors
Ras
overexpression of EGF receptor leads to ?
dimerization in the absence of EGF
? block dimerization of EGF receptor
monoclonal antibodies
SH2 and SH3 domains of Src work together to inhibit
tyrosine kinase activity
90% of patients with chronic myelogenous leukemia have a chromosomal defect that ?
activates a tyrosine kinase bcr-abl
? is an effective treatment for chronic myelogenous leukemia
gleevec