signal transdcution Flashcards
What are MAP Kinases
serine/threonine kinases involved in regulation of many cell processes. (proliferation,apoptosi)
which is the SH2 domain protein in map K
GRB- docks onto the tyrosine residues
core kinase in Map K
Ras
signalling molecule-MAP K
Growth factor e.g IGF 1 , EGF
What is the function of SOS
Guanine nucleotide exchange factor for RAS
what is the pathway of insulin?
Still tyrosine kinase but a special type
Pathway of insulin
- Insulin binds to alpha
- Dimerises - the b subunits have kinase activity its heterotetrameric 2 a and 2 b which are transmembrane
- Autophosphorylation
- Phosphorylates IRS1
- PI3K (phosphoinosittid 3 kinase)
- Pip 2 - Pip 3 -PDK1 (enzyme)- AKT/protein kinase B. (enzyme)
- AKT phosphorylates inhibitory proteinAS160 which usually prevent GLUT 4. Also phosphorylates GSK3 which is an inhibitor of glycogen synthase.
The role of insulin in signal transduction
Has a mitogenic function (MAP K)
and also pathway is metabolic effect (PI3K)
what kind of molecules are chemical messengers usually?
hydrophilic only 4 are hydrophobic
- steroid hormones
- active vitamins D and A
- Thyroid hormones
what mechanism do the hormones produced by the hypothalamus work with
Phospholipase C
relationship between PPP and Insulin
insulin activates PPP (anabolic)
GLUT 4 tissues
adipose, muscle, heart
GLUT 1
all cells, RBC - Insulin Independant
GLUT 3
brain, neurons, sperm. function in (hypo)
insulin indwpendant
high affinity, low KM
Explain MAP K
- ligand binds
- Dimerisation
- Autophosphorlation
- GRB 2 docks
- SOS binds
- RAS activated
- Kinase reaction
Glut 5
enterocytes of small intestine for the uptake of fructurse
GLUT 2
pancreas, liver, small intestine - (HYPER) low affinity and high KM -insulin independant
which pathway is associated with TYRK
JACK STAT- growth hormones
what are the molecules trigger JACK STAT
prolactin, GH, cytokines, INF
IL-6
pro inflammatory cytokine, associated with hepicidin which decreases iron levels by stopping ferroportin. Hepcidin increases when IL -6 is present. Hepcidin blocks fe release from liver and SI
JACK STAT
- cytokines and GH
- intracellular part of receptor associated with Jack (janus kinase)
- signal binds and the jacks phosphorylate each other
- Jacks phosphorylate Tyr
- causes STAT (TF) to bind to the Tyr
- JACK phosphorylates STAT
- STAT dissociates from receptor goes to nucleus binds ta response elements and activates gene transcription
Receptors with serine/threonine kinase activity
TGF -B receptors (transforming growth factors)
TGF receptor is complex, has 2 different receptor subunits. first 1 type 2 gets activated by the signalling molecule (TGF) then activates type 1 by phosphorylation at a ser residue.
type 1 binds to Smad (R-smad) which it phosphorylates at ser. R-smad dissociates from receptor and forms complex with co-smad. smad complex goes to nucleus to affect transcription.
Smads are gene specific TF’S
TGF is a hormone/cytokine involved in tissue repair, immune regulation , cell proliferation and bone morphogenic proteins (BMPS)
what does associeted TYR kinase mean
The receptor itself has no intrinsic kinase activity but binds the the tyrosine kinase JACK
Non receptor serine/threonine kinases
These are several serine/threonine protein kinases that are responsible for phosphorylating a variety of intracellular proteins on ser/thre residues. the most important are PK C A G
mtor
ser/thr kinase regulates autophagy, proliferation, protein synthesis transcriptpm. coded for by FRAP 1 gene. forms 2 different complexes. rapamycin is a bacterial toxin that inhibits mtor by binding to its intracellular receptor FKBP12
mtor integrates the signal pathways of insulin, growth factors (iGF 1/2_
PKG
directly stimulates
- synthesis of nO
- soluble intracellular Gunayl cyclase
INHIBITS phosphodiesterasde 5 - which selectively cleaves cgmp
PKG also modulates the PKG also modulates the intracellular concentration of intracellular concentration of
Са2+, which is a key ion for activity of , which is a key ion for activity of ( eNOS) and nNOS
NOS pathway
- stimulate muscle with ACH
- Ativates ca dependant NOS synthase
- gas so diffuses to muscle and you have soluable guanyl cyclase there. binds to it, turns GTP-CGMP-PKC G
- relaxation of smooth muscle by activation of myosin light chain phospahatse
PTEN
is a phosphatase which dephospharataltes PIP 3 thus inhibiting the PI3K pathway. its acts as a tumour supressor gene.
what is the signalling molecule for PI3K
insulin, growth factors like a PDGF,EGF
natriuretic peptide and receptors
It relaeases NA in urine
3 receptors
NPRA
NPRB
NPRAC- g protein linked and is a clearance receptor that internalises and destroys the ligand
which is the aa precursor for nO
arginine
plasma membrane receptors
- associated with ion channels
- associated with G proteins
- with intracellular domains with enzymatic activity
- tk activity
- tyrosine phosphatase
- serine/thr activity
- gunaylate cyclase activity - death receptors
- integrins
G proteins
so called as they bind to guanine nucleotides
heterotrimeric
Receptor spans the membrane 7 times
in its inactive state GS a has GDP bound
when ligand binds causes a conformational change replacement. the a subunit and GTP dissociate to go and activate adenylate cyclase
- ATP—-CAMP—PKA
- for response to stop GTP will be hydrolysed by GTPASE T then a will rejoin others.
example of g protein
adrenaline
different types of g proteins
- GS a-increases camp
- GI a- decreases camp
- GQ- involved in the ip3 pathway s
- Gt transducin
g transducin
responsible for generating the signal int he rods of retina in response to light. it stimulates CGMP phosphodiesterase (break down)
Regulation of glycogen synthase and phosphorylase
GS
:) - Insulin
:( glucagon and epinephrin
GP
:) glucagon and epinephrin
:( insulin
G protein that regulate ion channels
Muscarinic ACH receptor in the heart .
linked to K channels
when ACH binds stimulates the G inhibitory unit
now b and gamma dissociate, bind to channels increasing k permeability, hyperpolarizing membrane and decreasing frequency of contractions
rod cells
In dark, rod cells have a high level of cGMP which keeps the gates open (na)). When there is light activates opsin which cause sa displacement of gdp on a g protein called transdcucin. This activates Cgmp phosphodiesterase convertes CGMP-GMP leads to dissociation of cgmo from channeles leads them to close—–generate AP
second messangers
They amplify the signal because more of it is produced compared to the first messenger. they are short lived intracellular signalling molecules. removal of the 2nd messenger terminates the response
the communication between cells
- Ca
- No/co
- CAMP/CGM[
