L10 - TGF-B and FGF Signalling Flashcards
Three common features of signalling pathways
Reception
Transduction
Response
How many families of RTKs
20
In the human genome how many RTKS identified
58
Ligands which are specific for one receptor are
High affinity
Ligands which are specific for many receptors are
Low affinity
All RTKS are ______mers except
Monomers
Except insulin receptor
What domains vary greatly RE RTKS
EC domains
What is the EC domain of an RTK responsible for
Ligand binding activity
How many TMDs does an RTK have
1
RTK ligands able to
Dimerise
Binding of ligand to RTK fascilitates
Receptor dimerisations
Once the receptor has dimerised and is positioned correctly describe what happens
Kinase domains phosphorylate each other
What is the effect of the kinase domains phosphorylating each other
Increases the activity of the receptor
Stabilises the receptor in the active state
Causes the kinase domains to phosphorylate other tyrosines in the receptor
What is the effect of other tyrosines in the receptor being phosphorylated
Creates binding sites for other proteins with an SH2 domain
Describe how a dominant negative receptor tyrosine kinase would be made
Created RTK mutated in the kinase doamin
Dimerise with wildtype receptors (with an active kinase domain - poisons the endogenous receptor
Describe how you would make a consitiutively active RTK
Make DNA for a normal receptor which lacks a ligand binding domain and instead has a homodimerisation domain
RTK dimers form in the absence of the ligand - LIGAND INDEPENDENT
What three types of signalling molecule bind to the phosphorylated receptor
PI3-kinase
GTPase activating protein
PLC-gamma
PI3 kinase and PLC-gamma are part of which pathway
Inositol lipid pathway
SH2 doamins in SRc recognise which short polypeptide
Phosphotyrosine, glutamic acid, glutamic acid, isoleucine
What two domains does GRB2 contain
SH2 and SH3
What is Sos
Guanine nucleotide exchange factor
What is the effect of binding of GRB2 and Sos
Couple the receptor to the inactive Ras
What does Sos promote
Dissociation of GDP from Ras
Once GDP dissociated from Ras what happens
GTP binds - dissociates from Sos
When is Ras ON/OFF
ON with GTP bound
OFF with GDP bound