signal transduction 4 Flashcards
DAG and PIP3
plasma membrane second messenger
camp cgmp
h20 soluble second messneger
Ca
ion second messenger
ips
water soluble second messneger
arachnidoic acid
PM associated second messneger
tf Ca can be made and destroyed
F cant
Ca2+ ——- in the particular compartment of the cell is the signal detected by the next member in the signaling cascade.
Ca2+ concentration in the particular compartment of the cell is the signal detected by the next member in the signaling cascade.
tf cell quiet
When Ca2+ concentration increases (10-6 M or greater
F
When cytoplasmic Ca2+ concentration is low (10-7 M)
When Ca2+ concentration increases (10-6 M or greater), sensor molecules detect the rise and activate specific responses.
Cell activation depends on a —— between calcium—- and calcium- — mechanisms.
Cell activation depends on a balance between calcium-OFF and calcium-ON mechanisms.
2 ways Ca off mechanism remove Ca
pumping it from the cell
or back into internal stores
Na+ /Ca2+ exchanger (NCX)
or antiporter Ca2+ -ATPase (PMCA)
Plasma membrane proteins that are calcium pumps
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)
Intracellular calcium pumps
Low affinity
High transport rate
Na+ / Ca2+ Exchanger (NCX)
High affinity Low transport rate
Ca2+-ATPase (PMCA)
SERCA
Ca in with ATP breakage
TF CA binding proteins only exist in the SER
F in SER and cytoplasm(buffer action)
Calcium-ON mechanisms add Ca2+ to the cytoplasm from ——- sources and —– stores
Calcium-ON mechanisms add Ca2+ to the cytoplasm from extracellular sources and internal stores
(favored by large electrochemical gradient).
Calcium on mechanism that add Ca to cytoplasm
Ligand-gated ion channel receptors
cation selective
let Ca into cytoplasm
Voltage-gated channels
(action-potential responsive)
let Ca into cytoplasm
universal Intracellular calcium channels
1,4,5-Inositol trisphosphate receptors (IP3R)
skeletal and cardiac muscle Intracellular calcium channels
Ryanodine receptors (RyR)
AP or
voltage gated Ca channel
allow Ca into cell
Ryanodine Receptor (RyR)
and 1,4,5-Inositol Trisphosphate Receptor (IP3R)
both need to be triggered by Ca to release Ca from their compartments
Various —— -binding proteins act as molecular —– for detecting increased cellular concentration of —– .
Various calcium-binding proteins act as molecular sensors for detecting increased cellular concentration of Ca2+ .
Activated sensors stimulate a variety of —– proteins that regulate specific cellular functions.
Activated sensors stimulate a variety of downstream proteins that regulate specific cellular functions.
found in all cells where it mediates many regulatory pathways.
Calmodulin (CaM)
restricted to skeletal and cardiac muscle where it regulates contraction by controlling actin-myosin interaction
TnC
Two major Ca2+ sensors are
Two major Ca2+ sensors are tropinin C and calmodulin.
loops bind Ca
in Calmoduline
and middle alpha helix stretches
tf Ca2+/CaM-Dependent Protein Kinase is not at all active when it doesnt have Ca 2+ CaM attached to it.
F
it is 80% active although inh portion of it is free and open
Ca2+/CaM-Dependent Protein Kinase (CaM-Kinase II)
totally inactive when phospatase strips off PO4 from it3
bind inh domain of Ca2+/CaM-Dependent Protein Kinase (CaM-Kinase II)
Ca 2+/CaM
activation of Ca2+/CaM-Dependent Protein Kinase (CaM-Kinase II)
prompts autophos and Ca2+/CaM-Dependent Protein Kinase (CaM-Kinase II) is fully active
Tf 1st Ca is release then CaM is released from Ca2+/CaM-Dependent Protein Kinase when it is fully active
T renders it partially active
adenylate cyclase
converts ATP to cAMP
AC occurs at
PM
G-protein-coupled receptor act. by
Camp
cat domain of AC
b/n helix 6 and 7
TF both N and C terminal of AC exist intercellularly
T
AC
has 12 total alpha helix( transmembrane)
when ligand binds GPCR
G protein binds it
bind of g protein to GPCR
triggers GTP exchange on alpha subunit and it subsequently binds AC (PM)
Camp
binds reg. subunit of pka and dissociates catalytic subunit from regulatory
catalytis subunit of pKa
phos CREB and alters gene expression
gpcr1;gpcr2
g protein stim; g protein inh
+camp;- camp
Cholera toxin
has enzymatic activity that int with NAD in cyt.
Ox Nad when triggered by Cholera toxin will
transfer adp ribose on Arg on Gs subunit of G protein(cant longer use ATPase activity)
transfer of ADP ribose to ARg on Gs
inc camp by promoting irreversible binding of alpha subunit to AC(cant use Gtpase activity)
cholera
prolonged opening of Cl channels and inc. Pka activity
tf in cholera there is minimum loss of Na and water in intestines
F excessive
pertusssis toxin
transfer ADP ribose to Cys on alpha subunit of Gi
Gi cant bing AC and cant inh
inc Pka and camp exist in
cholera and pertussis
High insulin; low glucose (seizures)
High histamine; low pressure (shock)
Pertussis
TF hormone levels not affected in pertussis
F affected
termination of camp
pde converts it to 5’ amp
GC
converts GTP to cGMP
bind ssoluble GC on a heme
NO
binds to membrane ass GC
ANF
cGMP act
PKG
cGMP term to
5 gmp by cGMP Phosphodiesterase
Pi PE PC
polar head group of phosphpholipid
PIP2
Major Substrate for Producing Second Messengers
Phosphoinositide-4-Kinase
convert PI to PIP
PIP converted to PIP2 by
Phosphoinositide-5-Kinase
Activator of Ca2+ release from endoplasmic reticulum
IP3
phospholipase C
breaks PIP2 into DAG and IP3
DAG
Membrane bound
Activator of protein kinase C (PKC)
DAG
phsopholipase D
breaks PC into phosphatidic acid and choline
(1st step of DAG generation)
PAP
break phosphatidic acid ito DAG and PO4
(2nd step)
IP3 act
ip3sensitive channels to let out Ca
Ca bind protein kinase C which binds DAG (membrane) which phos substrates
Precursor for production of eicosanoids
Arachidonic acid (AA) –
phosphlipase A2
breaks PIP2 into AA(membrane bound)
and
PI
only has PO4 on 1 position
PIP
PO4 on 4 position
PIP2
po4 on 1,4,5 position
PIP3
Activator of kinases recruited to membrane
PI 3 kinase
puts po4 on 3 position
converts PIP2 to PIP3
tf phosphatase can convert PIP3 to PIP2 to PIP1 to PI
T
exist in cytoplasm
camp
cgmp
ip3
membrane
DAG
AA
PIP3
tf IP3 and PIP3 use PIP2 as a source
T
AA and DAG
use PC and PE as a source
uses PI PIP PIP2 as sources
AA
tf dag can use PIP2 as source
T
ATP;GTP as source
camp; cgmp
Forms eicosanoids
AA
Activates PKB, PDK1
PIP3
act. pkg;pkc
cGMP;DAG
act pka
camp
release Ca from ER
IP3
effector AC ; GC
camp; cgmp
Pla2 is effector enzyme for
AA
pi 3k effector enzyme for
PIP3
PLC is effector nzyme for
IP3 and DAG
PLD/PAP effector enzyme fore
DAG
GC effector enzyme for
cGMP
