Intracellular signaling

signal transduction

the process by which extracellular signals are communicated to specific domains within the cell

3 steps of signal transduction

signal, receptor, and target molecule

types of cell signaling

synaptic, paracrine, and endocrine

what is an example of a lipophilic organic molecule

Endocannabinoids (2-AG)

what are the 4 different receptor mechanisms

channel-linked receptors, enzyme-linked receptors, GPCRs, and intracellular receptors

what domains on GPCR make up the neurotransmitter binding region

II, III, VI, VII

what domains on GPCR does the G-protein bind to

VI and C terminus

what is the "off" state of the G-protein

when it is bound to GDP

what is the "on" state of the G-protein

when it is bound to GTP

what is the "Large" G-proteins

Heterotrimeric G-proteins

what subunits make Heterotrimeric G-protein

α, ß, and gamma,

what is the "small" G-protein and give an example

monomeric G-proteins, Ras

what does αi do

inhibitory alpha subunit -> inhibits Adenylyl Cyclase -> inhibits cAMP -> PKA

what does αs do

stimulatory alpha subunit -> stimulates Adenylyl Cyclase -> stimulates cAMP -> PKA

what does αq do

activates PLC (phospholipase C) -> IP3 and DAG -> IP3 release Ca++ from ER; DAG activates PKC (allows Ca++ into cell)

how to cAMPs activate PKA's

4 cAMP molecules bind to PKA releasing Catalytic subunits from inhibiting it

what does IP3 stimulate the release of

Ca++ from the ER

what does DAG activate and what does it do

PKC; Allows for Ca++ to enter the cell

Serine/Threonin kinases

PKA, PKC, and CaMKII

what do protein kinases do

enzymes that phosphorylate other protiens

what do protein phosphateses do

enzymes that remove phosphate from other proteins

what do catalytic subunits responsible for

transferring phosphate groups to Protein kinases

explain the autoinhibition of protein kinases

catalytic subunits are kept inactive by regulatory subunits

how does binding of a secondary messenger affect autoinhibition

second messenger (cAMP, DAG, Ca++) bind to protein kinase and remove autoinhibition, allowing catalytic domain to be activated

how many cAMP's are bonded to PKA to remove its autoinhibition

4

what kinase does Ca++ only activate

CaMKII

what kinases are activated by lipids AND calcium

PKC

what kinases are activated by EXTRAcellular ligands

TRKs

what kinases are activated by Lipids only

PDK1/AKT

what proteins on PKA do catalytic subunits phosphorylate

serine and threonine

what lowers the activation of PKA

Phosphodiesterase

what does phosphodiesterase do

converts cAMP to AMP

what does DAG cause PKC to do

move from cytosol to the membrane where it binds to Ca++ and another phospholipid (PS)

what happens when DAG, Ca++, and PS are bound to PKC

PKC is able to phosphorylate proteins

what activates CaMKII (Calmodulin dependent protein kinase type II) and how

Ca++/Calmodulin by displaying the inhibitory domain from the catalytic subunit

where are the intracellular stores of Ca++

ER and Mitochondria

what do MAPK (Mitogen-activated protein kinase) proteins do

phosphorylate transcription factors AKA regulate gene expression

what is special about MAPK

MAPK are kinases that themselves are activated by other kinases (MAPKKK -> MAPKK -> MAPK)

how do TRK's (tyrosine receptor kinases) work

once ligand is bound to receptors, receptors form a dimer and AUTOphosphorylate

once autophosphorylated, what do TRKs do

activate RAS-activating protein which activates RAS protein

examples of PPs (Phosphoprotein Phosphatase family)

PP-1, PP-2A, and PP-2B (*Calcineurin*)

what do Transcription Factors allow

RNA polymerase to assemble on the DNA promoter region to begin transcription

2 types of transcription factors

Transcriptional Activators and Transcriptional Repressors

what do Transcriptional Activators do

enhance gene expression

what do Transcriptional Repressors do

Decrease gene expression

what is CREB

cellular transcription factor

what does CREB bind to

bind to DNA sequences called CRE, either increasing or decreasing the transcription of the downstream genes

phosphorylation of what potentiates transcription

CREB

what are the activators of CREB

PKA, RAS/MAPK, CaMK-IV, and Ca++