Cell M2: Module 1 Flashcards
signalling with the most distance between cells
endocrine signalling
signalling where cells are a distance away from eachother (not farthest away)
paracrine signalling
An enzyme that takes a phosphate group from an ATP and adds it to serine, threonine or tyrosine
protein kinases
frequent way of modifuing target proteins, involves the addtion of a phosphate group to a serine, threonine, or tyrosine
protein phosphorylation
protein dephosphorylation, where a phosphate group is cleaved, is acmmonplished by who
phosphatase
ionotropic receptors structure:
4-5 sububits grouped around central pore
charge amino acids form selectivity filter
G-protein coupled receptors
metabotropic receptors
GPCR structure
span membrane 7 times
structiure of enzyme linked receptors
extracellular domain for ligan binding
intracellular domain for enzymatic activity
what is the normal enzyme activity of enzyme-linked receptors
usually a kinase activity
what do receptor tyrosine kinases do
phosphorylate substrates into tyrosine residues
what does serine/theronin receptor kinases do
takes phsophate from substrate and give to ser/thr residues
what do tyrosin and ser/thr phosphatases receptors do
enzyme linked recepts that give phosphate to substrates that have had one taken from them–> returning them back to their original form
how do enzyme-linked receptors work
ligand binding to extracellular domain activators receptor for anzymatic activity
intracellular receptors are located where:
cytoplam or nucleus
what activates an intracellular receptor
ligand, a small lipophillic signalling molecule that has crossed PM
when not ligan bound what happens to intracellular recepts
attached to inhibitory proteins
what receptors move to nucleus after dishibition after ligan binding
plasmic (cytoplasmic) intracellular receptors
what is the purpose of intracellular receptors
once theyre in nucleus they can bind to DNA and act as transcriptiona modulators for DNA by effecting prevelance of specific genes
proteins that are able to bind to and hydrolyze GTP
Gproteins
Classes of G proteins
heterotrimeric, and small monomeric
what are heterotrimeric g proteins activated by
GPCR receptor
hat ar esmall monomeric g protein receptors activated by
receptors tyrosin kinases which phosphorylates substrates to obtain a phosphate and then lets go of an adaptor protein which activates GEF
What inactivates heterotrimeric G proteins? how?
GAP- by cleaving a phosphate group of of GTP
What does Gs have an effect on
activates adenylate cyclase
What does Gi have an effect on
inhibits adenylate cyclase
What does Gt have an effect on
Activates phosphodiesterase
what does acitvated Phosphodilipase C effect
diaclglycerol goes up
IP3 goes up
What does adenylate cylase have an effect on
cAMP
What does phosphodiesterase have an effect on
inhibits cGMP
what does ras endpoint
MAP Kinase pathways
what is the rho endpoint
ROCK Kinase
What is the rab endpoint
various
what is the function of ras
cel proliferation, differentiation and survival
what is the function of rho
actin dynamics
what is teh function of rab
membrane trafficking
cAMP, cGMP, IP3 and DAG, and calcium are all _________
second messangers
what does cAMP have an effect on
Protein Kinase A
what can cAMP by degraded by
phosphodiesterase
what is protein kinase A made of
catalytic and inhibitory subunits
what happens to protein kinase A if cAMP binds
the inhibitory protein dissicociates from the catalytic
what is cGMP generated from
guanylyl cyclase after it is activated by GTP
what does cGMP have an effect on
Protein kinase G, and can bind to cyclic nucleotide gatd ion channels to open them
Are cGMP levels normally high or low? why?
high to keep cyclic nucleotide gated channels open
what signal causes the decreases of cGMP?
phosphodiesterase when Gt protein bound
what is the important second messanger for photoreceptor
cGMP
what does Phosphatidylinositol biphosphate (PIP2) generate? how?
IP3 and DAG when cleaved by phospholipase C
where is IP3 located
in the cytosol; second messanger
where is DAG located
plasma membrane
Where does IP3 go
binds to IP3 receptors in the ER, which when bound open to allow flow of calcium
what does DAG do
activates plasma membrane associated proteins like Protein Kinase C, which phosphorylate serine and threonine residues
what is calcium
a second messanger
What does CAlcium ATPase punmp ( PMCA) do
actively extruds Ca from cytoplasm
what does Na+/Ca2+ pump do
uses Na+ gradiant across PM to extrude calcium
What does sacro/endoplasmic reticulum calcium ATPase (SERCA) do?
uses ATP energy to take Ca2+ from cytoplasm into lumen in ER
What uptakes calcium from cytoplasm
mitochondria, SERCA
Where does Calcium come from in plasma membrane? sources of Ca2+ signals
Voltage gated calcim channels; ligand-gated Ca2+ channels
Where does Calcium come from in intracellular stores
IP3 receptors- in ER membrane; ryanodine recepts (calcium induced calcium release- amplifies calicum signal)
how does calcium ellicit a cellular response
calcium sesnors of calmodulin family (CaM) that bind calcium in a cooperative manner anf then can go bind and activate other proteins
What can calmodulin (CaM) bin and activate once it itself has been activated by calcium
enzymes like kinases and phosphatases
calcium channels
Calicum calmodulin dependent kinases
Explain CMKII
calcium calmodulin dependent kinase II, most import CaMK isoform; mosulates synaptic transmission by phosphorylating proteins
is CaMK normally active or inactive
inactive with regulatory and catalytic domain
what binds to CaMK to release regulatory domain from catalytic domain
Calmodulin
Increase of Protein Kinase A results in
increase protein phosphorylation
Calcium release and protein kinase C result in
increase protein phosphorylation and activate calicum binding proteins
why is signal tranduction gene expression requiring slow
is requires new mRNA synthesis but this is very long lasting
what are transcriptional activator and what doe they do
proteins that bind to specific DNA sequences and interact with general trnascription factors/ RNA polymerase to initiate synthesis of new mRNA
CREB is what
cAMP responsive element that is a transcriptional activator present in nucleus of cells
When can CREB bind to DNA in nucleus
when phosphorylated
what is CREB phosphorylated by-
protein kinase A
calcium camodulin dependent kinase
MAPK
c-fos
transcriptional activator present in unstimulated cellas at very low concentrations; immediate early gneer
genes for proteins present ni cells at very low concentrations only transcribed when activated. leads to transcription of other target gene
immediate early gene
