290119
Description
Flashcards by andreatong18, updated more than 1 year ago
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Created by andreatong18
over 10 years ago
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| Question | Answer |
| Receptor Enzymes | - Extracellular surface. - Intracellular surface. - insulin receptor is prototype. |
| Insulin Receptor | - Insulin regulates: i) metabolism, ii) gene expression. - Extracellular insulin signal -> insulin receptor -> insulin-sensitive metabolic enzymes -> nucleus -> gene transcription. |
| Structure 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. |
| Sequence 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. |
| Sequence 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. |
| Sequence 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. |
| Sequence of events # 4 | Raf-1 phosphorylates MEK. - MEK-P-P phosphorylates MAPK. - MAPK-P-P enters nucleus. |
| Sequence of events # 5 | - Activate Elk1-P binds SRF. - Elk-P-SRF stimulates transcription and translation of genes needed for cell division. |
| What 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. |
| # 2 | - Bound PIP3- PKB phosphorylated by PKD1. - PBK can phosphorylate serine and threonine residues on target proteins. - GSK3 is active without phosphorylation. |
| # 3 | active GSK3 phosphorylates glycogen synthase. - Non-phosphorylated GS -> active - Phosphorylated GS -> Inactive. - PKB phosphorylation of GSK3 prevents GSK3 phosphorylation of GS. |
| # 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. |
| SH2 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. |
| Receptor Kinases | - One activated receptor can activate several IRS-1 molecules. - IRS-1 can activate any SH2-domain proteins. |
| Nuclear Receptors | Bind to: - Steroids - Retinoids - Thyroid Hormones - Vitamin D |
| # 2 | - Used by steroid and thyroid hormones. - Are stimulated in nucleus. - active receptor stimulates gene transcription -> specific proteins are produced. -> proteins induce cellular effects. |
| # 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. |
| # 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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