Signal Transduction Flashcards
What is TGF-B?
A transforming growth factor - small protein hormone
What kind of signalling in TGF-B involved in?
Paracrine signalling
What is estradiol?
A steriod hormone
What kind of signalling is estradiol involved in?
Endocrine signalling
What are two differences between TGF-B and estradiol?
- TGF-B = protein encoded by a gene, estradiol = steriod synthesised by enzymes
- TGF-B cant cross cell membrane by estradiol can
What is signal transduction?
The molecular mechanism that converts a signal into a response - involves a ligand and a receptors and the receptor-ligand complex then initiates the response
How many nodal genes do humans have?
1
How many nodal genes does xenopus have?
6
What is nodal
Different levels of nodal related proteins in endoderm due to the gradient between B-Catenin and Veg-T leads to mesoderm induction differentially along the dorsal ventral axis
What are families/superfamilies?
Groups of related proteins and genes that encode them that are related by evolutionary ancestory
What is the general structure of a TGF-B family protein?
A signal peptide, a propeptide and a ligand
How many aa long is the signal peptide?
20aa
How many aa long is the ligand?
130aa
What happens to the signal peptide?
It is removed during translation by being pulled in the ER and cleaved before the rest of the protein is made
What is the proprotein?
The propeptide + the ligand - the propeptide is there to block the ligand activity
What happens to the propeptide?
It is removed outside of the target cell to allow the mature ligand to become the signal
What removes the signal peptide and the propeptide?
Proteolytic cleavage
How does TGF-B act as a signal?
It causes an allosteric change in shape of the receptor by acting as a serine/threonine kinase
Where do a protein kinase transfer the phosphate from?
From a high energy phospho-sugar source like ATP or GTP
What is the sequence of events from when TGF beta binds its receptor?
It binds and causes two receptors (type 1 and type 2) to dimerise which then phosphorylise (autophosphorylate) the serine/threonine/tyrosine residues on the receptors, the phosphorylated receptor then recruits smad2 and smad3 and causes it to oligomere with smad4 which can then go on to regulate gene transcription
What happens in cancer that involves TGF-B
They normally have a mutation in the smad proteins or in the TGB receptors and are resistant to growth inhibition by TGF-B
What do most pancreatic cancers have a mutation in?
The gene encoding smad 4
What cancers are resistant to TGF-B growth inhibition?
Retinoblastoma, colon, gastric, and some T and B cell malignancies
Describe the solubility of steriod hormones?
They are hydrophobic (water insoluble) but lipophillic so can cross the cell membrane
If steroid hormones are insoluble in water what are they carried by?
The serum albumin
What are the two intracellular receptors of estradiol?
Alpha and beta which dimer to have three different combinates (ERaa, ERab, ERbb)
What happens when estradiol binds its intracellular target?
It causes it to form the dimer which then goes on to attach to the DNA and bind at hormone response elements (estrogen response element which is a palindromic sequence)
What causes different cells to repond to estradiol differently?
They amount/number/type of receptors they have
What is a common response to estradiol gene regulation?
Cell growth and division
How is estradiol linked to breast cancer?
There is an increased abudance of estradiol receptors in a lot of breast cancer as tumours use them to rapidly proliferate
What is a drug that could block the ER and therefore be used to treat present cancer?
A estradiol receptor antagonist like tamoxifen
