Intracellular signaling flashcards
Agonist
Molecule that activates responses associated with occupation of receptor
Antagonist
Molecule that prevents responses associated with occupation of receptor
Angiotension II receptor antagonists
Lower peripheral blood pressure
Glucagon-like peptide receptor agonist
Increases insulin secretion
2 types of receptors for secreted molecules
- Cell surface receptors 2. Intracellular receptors
Cell-surface receptors
Used by molecules which can’t cross the membrane due to size or charge
Integral membrane proteins
Cell-surface receptors which are coupled to intracellular molecules. Ligand binding to receptor initiates signal transduction cascade/pathway.
4 things that can bind intracellular receptors
Hydrophobic molecules which can bind to cytosolic or nuclear proteins 1. Steroid hormones 2. Vitamin D3 3. Reinoic acid 4. Thyroid hormones
First messenger to second messenger signaling
Extracellular binding is first messenger. Binding of molecule to receptor activates 1st intracellular molecule in cascade called the second messenger which activates the enzyme cascade
4 classes of cell surface receptors
- Ligand-gated ion channel 2. Enzyme-linked 3. Cytokine 4. G-protein-coupled
Receptor tyrosine kinases
Amino terminal is extracellular and carboxyl terminal is intracellular and catalytic. Enzyme effector is a component of the receptor protein
Non-receptor tyrosine kinases
Enzyme effector is a receptor complex
Adenyl cyclase
Enzyme effector is a non-receptor integral membrane protein
5 second messengers
- Ca2+ 2. 3’,5’-cyclic AMP 3. 3’,5’-GMP 4. 1,2-diacylglycerol (DAG) 5. Inositol 1,4,5-triphosphate (IP3)
3 amino acids which can be phosphorylated
- Serine 2. Threonine 3. Tyrosine
3 ways to terminate signal transduction
- Reducing agonist (ligand) availability 2. Internalizing and degrading of agonist-receptor complex 3. Modifying receptor to inactivate it
Receptor Tyrosine Kinase and Mitogen Activated Protein (MAP) kinase cascade steps
- Receptor binds to extracellular portion of RTK 2. RTK activated by phosphorylation 3. Adapter protein activates Ras-activating protein which activates Ras with GTP 4. Ras activates MAP kinase kinase kinase with ATP 5. Activates MAP kinase kinase with ATP 6. Activates MAP kinase with ATP 7. Nuclear gene regulatory protein OR cytosolic/membrane protein phosphorylated 8. Changes in gene expression OR rapid changes in activity of cytosolic/membrane proteins
Receptor serine-threonine kinases (3)
- Stimulated by growth regulatory families 2. Mutations in these receptors result in progression of cancer 3. Regulate SMAD transcriptional factors
Cytokine receptors
Lack intrinsic kinase activity. Dimerize and bond to non-receptor tyrosine kinases. Regulate STATs transcription factors
Cytokines
Polypeptides which are autocrine/paracrine regulators of growth and differentiation.
G-protein-coupled receptors (GPCR)
Alpha (many kinds), beta, and gamma subunits. Bind a diverse group of ligands. 7 alpha-helical transmembrane-spanning domains. Intracellular domains bind G-proteins. Activate Phospholipases and Rho GEF.
Adenyl signal transduction
Causes increase/decrease in cyclic AMP depending on signal from G proteins.
cAMP signaling 3 steps
- Uses adenyl cyclase (membrane bound) to activate Protein kinase A (PKA) by converting ATP to cAMP 2. cAMP activates PKA which phosphorylates CREB 3. Activated CREB binds to CRE which targets a gene for synthesis of cytosolic or membrane protein
Protein kinase A (PKA)
Contains a nuclear translocation sequence. Within the nucleus phosphorylates CREB (cAMP-responsive element binding) which binds to CRE (cAMP-responsive regulatory elements on gene promoter)
