Flashcards
Receptors linked to kinases and nuclear receptors
Cards in this deck (18)
- 1Receptor Enzymes- Extracellular surface.
- Intracellular surface.
- insulin receptor is prototype. - 2Insulin Receptor- Insulin regulates: i) metabolism, ii) gene expression.
- Extracellular insulin signal -> insulin receptor -> insulin-sensitive metabolic enzymes -> nucleus -> gene transcription. - 3Structure of Kinase-Linked Receptor- 2 identical a-chains.
- 2 identical B-subunits.
- Insulin binds at a.
- PK activity on B-subunit.
- PK activity transfers phosphoryl group from ATP to OH of tyrosine residues on terget proteins. - 4Sequence of Events # 1- Insulin binds a-chain of receptor.
- Tyrosine kinase activity of B-Subunit activated.
- Each aB monomer phosphorylates tyrosine residues on the B-chain of its partner in the dimer.
- Opens up active site -> tyrosine residues on other proteins can be phosphorylated. - 5Sequence of events # 2- Insulin receptor substrate-1 is a target protein.
- receptor phosphorylates IRS-1 on tyrosine residues.
- A tyr-P residue in IRS-1 interacts with a protein called Grb2. - 6Sequence of events # 3- Grb2 binds Sos.
- Bound Sos catalyses replacement of bound GDP with GTP on a protein called RAS.
- RAS-GTP can bind and activate a protein kinase -> Raf-1. - 7Sequence of events # 4Raf-1 phosphorylates MEK.
- MEK-P-P phosphorylates MAPK.
- MAPK-P-P enters nucleus. - 8Sequence of events # 5- Activate Elk1-P binds SRF.
- Elk-P-SRF stimulates transcription and translation of genes needed for cell division. - 9What else does phosphorylated IRS-1 do?- IRS-1-P binds PI-3 kinase.
- Activate PI-3K phosphorylates phosphatidylinositol 4,5-biphosphate.
- PIP3 binds another protein kinase. - 10# 2- Bound PIP3- PKB phosphorylated by PKD1.
- PBK can phosphorylate serine and threonine residues on target proteins.
- GSK3 is active without phosphorylation. - 11# 3active GSK3 phosphorylates glycogen synthase.
- Non-phosphorylated GS -> active
- Phosphorylated GS -> Inactive.
- PKB phosphorylation of GSK3 prevents GSK3 phosphorylation of GS. - 12# 4- Non-phosphorylated GS continues to convert glucose into glycogen.
- PKB also triggers glucose transporter movement.
- GluT4 moves from internal vesicles to plasma membranes.
- Stimulation of blood glucose uptake. - 13SH2 Domain Proteins- Src homology 2.
- Amino acid sequence of SH2 domains similar to a domain in another protein tyrosine kinase called Src.
- SH2 domains found in other signalling proteins.
All bind to tyr-P on another protein. - 14Receptor Kinases- One activated receptor can activate several IRS-1 molecules.
- IRS-1 can activate any SH2-domain proteins. - 15Nuclear ReceptorsBind to:
- Steroids
- Retinoids
- Thyroid Hormones
- Vitamin D - 16# 2- Used by steroid and thyroid hormones.
- Are stimulated in nucleus.
- active receptor stimulates gene transcription -> specific proteins are produced.
-> proteins induce cellular effects. - 17# 3- All nuclear receptors have a DNA-binding domain.
- Ligand binding domain is downstream from DNA-binding domain.
- Upstream from DNA-binding domain is a region that controls gene transcription. - 18# 4- Steroid binds receptor
- dimers bind to hormone response elements of nuclear DNA.
- HREs are 200 bp upstream from target genes.
- Response is an increase in RNA polymerase activity -> extra mRNA produced.
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- Pharmacology Flashcards on Receptors linked to kinases and nuclear receptors, created by andreatong18 on 20/10/2013.
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- andreatong18 · Oct 2013
- Updated
- Feb 19, 2016
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