signal transdcution Flashcards
(40 cards)
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