Membrane structure and function III Flashcards
What are some types of tyrosine kinase receptors
- Insulin
- Epidermal growth factor (EGF)
- Platelet derived growth factor (PDGF)
What does Jak-STAT signalling regulate
- Growth hormone
2. Interferon
What is a type of serine/threonine kinase receptor
TGF beta receptor
How are tyrosine receptors dimerised
- The 2 identical receptor molecules will dimerise after ligand binding makes a conformational change
- When the 2 molecules come together, signalling proteins cross link the receptors
How do tyrosine receptors become phosphorylated
The dimerisation brings together elements of the molecules, allowing them to modify each other
Phosphorylation occurs on specific tyrosine residues on the receptors through auto-phosphorylation
What happens after phosphorylation of the dimerised receptors
This creates further conformational changes that gives the receptor a docking site for other proteins
This could induce more phosphorylation and more protein binding and the chain reaction goes on
Activated tyrosine receptor; RAS protein pathway
- Grb-2 binds to the SH2 domain of the activated receptor causing a conformational change
- This allow Ras GEF to binds to the Grb-2 on its SH3 domain
- Ras GEF phosphorylates GDP bound on the RAS-GDP complex, making it a GTP
- Activated RAS protein will initiate a a number of different signals
Activated tyrosine receptor; PKB pathway
Tyrosine phosphorylation will cause PI 3-Kinase to be activated
This phosphorylates PIP2 to PIP3
PDK1 can bind to PIP3, causing it to activate and phosphorylate protein kinase B (PKB)
What will activated protein kinase B do
It will dissociate and activate other molecules in the cytosol
Where is the insulin receptor located and what does it do
Acts on the liver and muscle to reduce blood glucose
Whats the structure of the insulin receptor
Consists of 2 alpha and 2 beta subunits linked by disulphide bridges
What does binding on the insulin receptor cause
Auto-phosphorylation of the 2 beta subunits
What does phosphorylation of the insulin receptor cause
Activation of a large protein substrate - IRS
activated IRS activates PI 3-Kinase, which activates PKB
activates PKB will have effects of synthesis of glycogen and proteins
How are activated proteins disabled
Phosphatases are activated as a result of the receptor activation
They will remove phosphates therefore deactivating the proteins
How is PKB deactivated
P10
How are GTP binding proteins deactivated
They have intrinsic GTPase activity so deactivate over time
How is RAS protein activation regulated
Guanine nucleotide exchange factor will take inactive GDP and replace it with GTP
Activation of RAS will activate GTPase activating protein (GAP)
This will increase the GTPase activity on the RAS protein therefore speeding up the dephosphosphoryaltimn of GTP to GDP therefore deactivating the RAS protein
How can mutations in key regulatory mechanisms lead to cancer
Loss of GTPase activity or phosphatase activity could cause unregulated activation
Also over expression of EGF receptors can lead to breast cancers
Jak-STAT signalling pathway process
Ligand binding to the receptor causes Jaks to cross phosphorylate each other on tyrosines
Activated Jaks phosphorylate receptors on tyrosine
STAT1 and STAT2 dock on phosphotyrosines
Jaks phosphorylate STAT1 and STAT2
STATs disscoate from the receptor and dimerise via SH2 domain
Dimer will move into the nucleus and cause an increase in specific genes transcription
Smad-dependant signalling pathway
TGF-beta will initially bind to the type II TGF-beta receptor
This will allow for the association of type I TGF-Beta receptor to the type II
This will lead to the phosphorylation of type I
Smad 2 and smad 3 will be phosphorylated and activated
This will activate smad 4
A heterodimer will form
This heterodimer will go into the nucleus and it will regulate gene expression
