ENI - Hormones and Cell signalling 2 Flashcards
List water soluble hormones
- Serotonin
- Melatonin
- Histamine
- Adrenaline
- Noradrenaline
- Thyroid stimualting hormone
- Human growth hormone
What hormones exclusively use the adenyl cyclase signal transduction pathway?
- ACTH
- ADH
- FSH
- LH
- TSH
What hormones exclusively use the phospholipase C signal transduction pathway?
Hypothalamic Hormones:
- TRH
- GnRH
What hormones exclusively use the tyrosine kinase signal transduction pathway?
- Insulin
- Prolactin
- Growth Hormone
- IGF
What hormones exclusively use the guanylyl cyclase (cGM) signal transduction pathway?
- rare ANP
List lipid soluble hormones
- Steroid hormones
- Thyroid hormones
- Retinoids
- Vitamin D
- Cortisol
Describe receptor tyrosine kinases
- Most abundant group of enzyme linked cell surface receptors
- Intracellular domain has multiple tyrosine residues that can be altered by phosphoryation
- Varying extracellular domains to discriminate between signalling molecules
Describe signalling via receptor tyrosine kinases
- 2 ligands bind to 2 adjacent receptor chains, form dimer
- Activates intracellular tyrosine kinase domain
- Activated kinase domain transfers phosphate group from ATP to selected tyrosine side chains on receptor and subsequent signalling proteins that bind to phosphorylated receptors
Outline how signals can be integrated
- Different receptors bind different ligands
- Have different intracellular effects
- Converge at certain points, e.g. may both activate phospholipase C pathways
How is Ras regulated?
- Inactive when bound to GDP
- Active when boudn to GTP
- Carried out by GEF (guanine exchange factor)
Describe how Ras is activated by hormones
- Hormone binds to receptor tyrosine kinase, dimerisation occurs
- Autophosphorylation of tyrosines
- Grb-2 binds
- Regulates Ras GEF
- Actigvated, swaps GDP on Ras for GTP
- Activates Ras
- Ras transmits signal
How can Ras lead to different responses to hormonal stimuli?
- Different types of Ras
- Different degrees of Ras expression in cells
What is the role of the PI3-kinase pathway?
Regulates cell growth and survival (inhibition of apoptosis)
Describe the PI3-kinase pathway
- Activated by binding of insulin to RTK
- Activates (phosphorylates) protein kinase B (Akt)
- Akt phosphorylates mTOR (kinase) which stimulates proliferation
- Akt phosphorylates factors of Bcl-2 family which inhibits apoptosis
Describe the role of MAPK insulin activity
Through MAPK pathway: insulin promotes cell growth and inhibits gluconeogenesis
Describe the role ofthe PI3K pathway in insulin activity
- Through PI3K pathways insulin:
- Inhibits gluconeogenesis and glycogenolysis
- Induces translocation of glucose transporter (GLUT-4) to membrane (more uptake)
- Stimulates AA uptake and protein syntehsis
- Stimulates lipid synthesis and inhibits lipolysis
How is the phorphorylation cascade regulated in insulin signalling?
At each stage have protein phosphatases that inactivate that kinases produced at each step in order to downregulate
How is insulin resistance linked to receptor tyrosine kinases?
- IR may be due to loss of receptors
- May be due to loss of relay proteins (Ras)
Outline the receptor tyrosine kinase in relation to oncology
- Overstimualtion leads to cell growht and proliferation
- Inhibition of apoptosis
- Loss of control of growth and so tumours form
What is the role of effector proteins in intracellular signalling?
- Stimulated/activated by the signal transduction pathways
- Translocate to nucleus
- Modulate gene expression
- Modulate gene expression by binding of effector protein to “signal response element” on gene promoters
