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Describe the basic sequence of a generic signaling cascade: 4 steps and 4 outcomes
- 1. Hormone binds to EC part of receptor activating
- 2. Transducer (ex. G protein) which either directly activates protein kinase or activates
- 3. Effector enzyme which then activates protein kinase
- 4. Protein kinase phosphorylates hydroxyl group of target protein, leading to:
- Change in:
- 1. Enzyme activity
- 2. Protein-protein interactions
- 3. Transporter activity
- 4. Gene expression
Name the types of regulation (5)
- first three, from fastest to slowest and name timepoints.
- last two - give examples
- 1. Allosteric - immediate (effector changes shape of substrate binding site)
- 2. Covalent modification (i.e. (de)phosphorylation) of proteins catalyzed by protein kinases & phosphatases. seconds to minutes. Phosphate's negative charge alters enzyme shape/conformation.
- 3. Gene expression - hours to days.
- 4. Permanent compartmentation (DNA transcription is only in nucleus)
- 5. Variable compartmentation (GLUT 4)
Which amino acids can be phosphorylated? By which enzymes?
- 1. Threonine, serine, and tyrosines of certain proteins.
- 2. PKA, PKC, and calmodulin activated kinase.
What type of receptor is the insulin receptor? The glucagon receptor?
Insulin receptor - single spanning receptor w/ tyrosine kinase activity.
Glucagon receptor - 7-transmembrane G-protein coupled receptor
What protein activates recruitment of GLUT 4 transporters from IC pool to cell membrane? What facilitates activation of original protein?
- (1) Insulin binds to EC domain of single spanning receptor
- (2) Insulin binding causes change in conformation of receptor
- (3) This leads to autophosphorylation of tyrosines on IC domain (B-subunit) of receptor
- (4) Tyr-P phosphorylate tyrosines on IRS (Insulin Receptor Substrates) esp 1 &2.
- (5) IRS activates PIK3 which phosphorylates PIP2 to PIP3.
- (6) PIP3 goes on to either activate Akt or recruit glucose transporters (GLUT 4) to membrane .
T or F: Is dimerization necessary for the insulin receptor to work?
What types of effects does insulin have? How long?
Has covalent modifications (in the form of phosphorylation) which take minutes to hours.
Also affects gene transcription, which can take hours to days.
How are actions of insulin terminated?
By dephosphorylation of receptor
Name tissues that have insulin-independent systems:
- cardiac tissue, cells of nervous system, erythrocytes, cornea, muscle, hepatocytes, renal tubules, intestinal mucosa, etc.
- LIVER, HEART, SKELETAL MUSCLE, BRAIN, FAT