LECTURE 4 - hormone action and synthesis Flashcards
What are the hormone superfamilies?
Peptide
Steroid
Amino acid derivatives
How can hormones affect proteins?
FAST response = modify proteins (i.e. phosphorylation) - takes seconds-mins
SLOW response = activate new gene to make new protein (altered gene transcription) - takes mins-hours
What are the properties of a hormone receptor?
- must be visible to hormone
- binds hormone specifically and be able to detect it among other related molecules
- bind the hormone with enough affinity to detect hormone in the blood
- must only be on specific tissues
- must be saturable and must have limited number of binding sites (prevents constant activation, allows reaction to speed up and slow down and allows reversibility)
- must mediate some biological response
What are the 2 types of hormone receptors?
- Cell surface receptors
(either linked to TK or G proteins) - Intracellular receptors (steroid hormone receptors)
What are the subgroups of cell surface receptors linked to TK?
- Growth factor receptors (intrinsic TK) e.g. insulin, IGF1. EGF - all have TK domain built in
- Cytokine receptors (recruit TK) e.g. growth hormone, prolactin, leptin
What is TK?
Tyrosine kinase
- an enzyme that transfers a phosphate group from ATP to a tyrosine residue in a protein (phosphorylation)
- phosphorylation induces conformational changes
- TK activity can be either intrinsic or recruited
What are the properties of the extracellular EGF receptor?
EGF = epidermal growth factor receptor
- 4 family members (EGF 1-4)
- ligand-induced dimerisation: peptide ligands cleaved to yield active hormone
- autocrine, paracrine cell signalling
- signal transduction processes
- -> Ras
- -> Phosphatidylinositide 3-kinase (PI 3-kinase)
- -> JAK-STAT
Define autocrine and autocrine signalling
Autocrine = a substance that has an effect on the cell by which it was produced
Autocrine signalling = a form of cell signalling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell, leading to changes in the cell
Define paracrine and paracrine signalling
Paracrine = referring to a hormone that only has effect in the vicinity of the gland secreting it
Paracrine signalling = a form of cell signalling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells
What is the EGF receptor composed of?
- hormone binding site
- 2 cysteine-rich regions
- a single trans-membrane region
- kinase domain
Describe the basic mechanism of receptor modification
- hormone binds to receptor –> dimerisation = allows conformational shape change
- -> exposes kinase domain
- exposed kinase domain allows for phosphorylation to occur
- activation now allows for receptor to recruit other molecules (e.g. GRB + SOS)
- factors can enable second messenger pathway (e.g. by activating Ras) leading to activated transcription factors
How do receptors normally work?
- work as dimers
- dimerisation allows for conformational shape change
- exposes kinase domain –> allows for phosphorylation –> then activated to recruit other factors
What is Ras?
- family of related proteins all belonging to a class of proteins called small GTPase
- exists in 2 forms - 1 bound to GTP and 1 bound to GDP, becomes active when bound to GTP
Explain how recruited tyrosine kinase activity works
- receptors that do not have TK domain built in but still want to be able to phosphorylate
- use a secondary system (JAK-STAT)
JAK = kinase, STAT = transcription factor - cytokine hormone binds to receptor = induces shape change
- shape change allows for recruitment for JAK
- JAK phosphorylates receptor, can then recruit STAT molecule which affects transcription
What are G protein coupled receptors composed of?
- much more complex than those linked to TK
- 7 transmembrane domains
