Ch. 8 Flashcards
What are the 5 classes of receptor proteins?
- G-protein coupled receptors (GPCR)
- Receptor tyrosine kinases (RTK)
- Tumor necrosis factor receptors
- Nuclear receptors
- Ligand-gated ion channels
What are nuclear receptors?
- Intracellular receptors (hydrophobic)
- Not bound to membrane
- Serves are transcription factors that regulate gene expression
What are the steps of cell signaling that use membrane-bound receptors?
What are the steps of cell signaling that use nuclear receptors?
What are the results of cell signals?
How could you a Western to detect steps of cell signaling?
How could you use coimmunoprecipitation or immunoprecipitation with respect to cell signaling ?
How are Northern vs Western techniques applied to cell signaling?
Northern
- Specific RNAs (separate RNA by size)
- After electrophoresis and transfer to membrane paper and use nucleic acid probe
Western
- Specific protein (denatured, not native)
- Use antibody after SDS PAGE and transfer to a membrane
Compare and contrast endocrine, paracrine and autocrine signaling.
- Endocrine: near
- Paracrine: far
- Autocrine: self
What is endocrine signaling?
A hormone secreted into the circulatory system by a gland that can bind to a receptor protein on a target cell
What is paracrine signaling?
A hormone that functions over short distances to activate receptors on NEARBY cells
What is autocrine signaling?
A hormone that functions over short distances to activate receptors on the SAME TYPE of cell
What are first messengers?
- Extracellular ligands the bind to receptor proteins
- Categorized as endocrine, paracrine, autocrine
List examples of first messengers.
Hormones: biologically active compounds that are released into the circulatory system and come into contact with hormone receptors in target cells
What are second messengers?
Small, nonprotein intracellular molecules that amplify receptor-generated signals
List examples of second messengers.
- cGMP
- cAMP
- DAG
- IP3
- Ca2+
What 3 secondary messengers come from glycerophospholipid cleavage? End result?
- DAG
- IP3
- ???
What are the steps of the GPCR signaling pathway?
- Ligand-induced conformational changes in the GPCR
- Receptor-mediated stimulation of guanine nucleotide exchange (GTP replaces GDP)
- Regulation of downstream effector processes by Ga-GTP and GBy complexes
- Termination of signal
What are the steps of the RTK signaling pathway?
- Transmits extracellular signals by ligand activation of an intrinsic tyrosine kinase function found in cytoplasmic tail of the receptor
- Activated RTKs are dimers, which phosphorylate themselves before adaptor proteins link them to GEF for RAS
- Phosphorylate downstream signaling proteins that bind to RTK phosphotyrosines
How do ligand gated channels work?
Control the flow of of K+, Na+, and Ca2+ ions across the cell membrane in response to ligand binding
What is protein kinase A?
- Active when cAMP levels are hgih
- Leads to three distinct metabolic responses:
1. Phosphorlyation and inhibition of glycogen synthase; impedes glycogen synthesis
2. Phosphorlyation and activation of enzymes involved in glycogen degradation to produce glucose
3. Phosphorylation and activation of enzymes involved in gluconeogenesis (glucose from citric acid cycle intermediate and pyruvate)
What is phospholipase C?
A membrane-associated enzyme that hydrolyzes PIP2 to form DAG and IP3
What is GEF?
- Guanine nucleotide exchange factor
- Promote GDP-GTP exchange
- Activate signaling
What is GAP?
- GTPase activating proteins
- Stimulate intrinsic GTP hydrolysis activity
- Inhibit signal transduction
What are the 3 subunits of trimeric G proteins and which nucleotides bind when active vs inactive?
- α, Gβ, and Gγ subunits
- ???
How is Insulin involved in cell signaling and what pathway?
- Insulin (ligand) binds to the insulin receptor and induces a conformational change
- Insulin contains two chains, which are held together by disulfide bonds
How is cell signaling involved in cancer?
- The most common oncogenic Ras mutation lead to defects in the intrinsic GPTase activation and thereby block Ras protein inactivation. Dominant Ras mutations in the GTPase domain lead to chronic stimulation of the MAP kinase signaling pathway, even in the absence of growth factors
