biosignaling Flashcards
6 features of signal transduction
- specificity
- amplification
- modularity
- desensitization/adaptation
- integration
- localization
4 major types of receptors
- GPCR (G-protein coupled-receptor)
- receptor enzyme (tyrosine kinase)
- gated ion channel
- nuclear receptor
7 steps of GPCR
- epinephrine binds to its specific receptor
- GDP bound to Gsa and activates in GTP
- Gsa separates from Gsb, moves to adenyl cyclase and activates it
- catalyzation of cAMP by adenyl cyclase
- cAMP activates PKA
- phosphorylation of cellular proteins by PKA
- cAMP is degraded
what activates the PKA
cAMP
5 components of PKA
- regulatory subunit
- catalytic subunit
- substrate-binding cleft
- AKAP
- dimerization domain
what cause the cAMP to the PKA
when cAMP binds to the R subunit, it undergo a conformational change that moves the autoinhibitory domain of R out of the catalytic domain of C and the complex will dissociateto yiel 2 free catalytically active C subunits
signal control - termination 1 ,what are the two proteins that transform ATP to cAMP and cAMP to AMP
- adenyl cyclase
2. cyclic nucleotide phosphodiesterase
two exampls of modulators of GTPase activity (that can speed up or slow down the conversion of GTP to GDP)
- GAP : GTPase activator protein
2. RGS: regulator of Gprotein signaling
what are Raf, cGMP PDE, AC…
downstream effector enzymes
in the desensitization, what do Bark (b-adrenergic receptor kinase)
it phosphorylates the Ser residues at the carboxyl terminus of the receptor
what do the Barr (B-arrestin)
it binds to the phosphorylated carboxyl-terminal domain of the receptor
how the receptor-arrestin enters in the cell
by endocytosis
4 different localization of a signal
plasma membrane
nucleous
mitochondria
ion channels
what activates phospholipase C (PLC)
Gqs linked to GTP
what PLC catalyzes
the production of 2 second messenger:
- diacyglycerol
- cleaves PIP2 to IP3
real name of IP3
inositol 1,4,5-triphosphate
what do IP3 (which is water soluble)
it diffuses from the plasma membrane to the endoplasmic reticulum where it will bind to a specific receptor-gated Ca2+ channel, causing it to open
what do Ca2+ and diacylglycerol
activates PKC (protein kinase C)
2 major pathways activated by tyrosine kinase receptors
- MAPK
2. PIP3
composition of the receptor tyrosine kinase
- ligand-binding sites on the extracellular domain
- a single transmembrane helix
- a cytoplasmic domain with protein Tyr kinase activity controlled by extracellular ligand
why the macanism of activation of INSR, PKA and PKC are similar
because in every case, a region of the cytoplasmic domain that usually lock the active site is moves out after being phosphorylated
what the activation of the receptor tyrosine kinase allows
it allows to B subunits to phosphorylate the three Tyr residues on the other B subunits and the three highly charged P-Tyr force a change in the position of the activation loop, away from the substrate-binding site, which become available to bind and phosphorylates target protein
what insulin receptor phosphorylates
IRS-1 on its Tyr residues
MAPK- what bind to the P-Tyr of IRS-1
SH2 domain of Grb2. Then Grb2 binds to Sos and then Ras (will cause the change GDP to GTP). so, the order is:
IRS-1, Grb2, Sos, Ras binds to GTP
MAPK- activated Ras binds and activates what
Raf-1
MAPK- Raf-1 phosphorylates ______________ activating it. ___ phosphorylates _____, activating it
- MEK on two Ser residues
2. ERK, on a Thr and Tyr residue
MAPK- where the ERK moves and what does it phosphorylates
moves to the nucleous and phosphorylates nuclear transcription factors such as Elk1 (active them)
PIP3- what IRS-1 activates
PI3K by binding to its SH2 domain
PIP3- What PI3K converts
it converts PIP2 to PIP3
PIP3 bound to what
PKB which is phosphorylated by PDK1
what PKB phosphorylates
GSK3 on a Ser residue, inactivating it
what GSK3 can’t do when it is in its inactivate form
it cannot convert glycogen synthase (GS) to its inactive form by phosphorylation so GS remains active
what PKB stimulates
the movement of glucose transporter GLUT4 from internal vesicle to the plasma membrane, increasing the uptake of glucose
cross integration : effect of INSR to adrenergic receptor
- when INSR is activates, its Tyr kinase phosphorylates B-adrenergic receptor on two Tyr residues near the carboxyl terminus + indirectly through activation of PKB that causes the phosphorylation of two Ser residues
* * effect: lowering the cell’s sensitivity to epinephrine - P-Tyr residues of the adrenergic receptor serve as nucleation point for SH2 domain-containing such as Grb2. Activation of the MAPK ERK is very greater in presence of B-adrenergic receptor
what is protein phosphorylation
it is the process in which a phosphoryl group (phosphate), donated by ATP, is transfered to an acceptor protein
** catalyzed by a protein kinase
what makes ion channels open
ligands or change in membrane potential
what do Na+K+ATPase
maintain the membrane in polarized state (-70 to -50 mV)
the direction of the ion depends on what
its electrochemical gradient
- the concentration of the ion on two sides of the cell
- difference in electrical potential
how voltage-gated Na+ channel and what it will cause
open when there is a stimulus that depolarized the membrane
- in response to the depolarization of Na+ inside the cell, voltage-gated K+ will open a short time after to repolarize the cell
what makes the voltage-gated Ca2+ channel and what it will cause
the wave of depolarization
it will triggers the release of acetylcholine by exocytosis into the synaptic cleft
what are the receptors (acetylcholine) for cations and anions
cations: serotonin and glutamate receptors
anions: glycine receptors
4 ligands for nuclear receptors
vit D, retinoic acid, steroids,thyroid hormones
when they are bind to their ligands and that they did their dimerization, nuclear receptors inside the nucleous will bind to what
to a specific regulatory regions called hormones-receptor elements (HREs) in the DNA adjacent to specific genes
nuclear receptors attract what
coactivator or corepressor protein and with them, regulates transcription of the adjacent genes, increasin or decreasing the rate of mRNA formation
6 types of signals cells receive from the environment beyond the plasma membrane
hormones neurotransmetteurs pheromone touch light antigens
definition of receptor
a membrane-bound or soluble protein or protein complex, which exerts a physiological effect (intrinsic effect) after binding its natural ligand
