CHAPTER 11 cell signaling I. Local regulators Ex) growth factors – paracrine signaling and neurotransmitters -synaptic signaling II. Long distance signaling - Hormones (insulin, ethylene) - nervous system as a whole 3 stages of signaling Earl Sutherland (1971) Epinephrine and glycogen breakdown 1) Reception – binding to signal receptor 2) Transduction-often a series of changes (signal transduction pathway) 3) Response-end result – a specific cellular response Receptor types I. Bound to plasma membrane G protein couple receptors Receptor Tyrosine Kinases Ion channel receptors II. Intracellular Located in cytosol or nucleus -require hydrophobic or small messengers Steroid hormones, thyroid hormones, NO Membrane receptors up close • G Protein-Coupled receptors widespread, very common, involved with many hormones (epinephrine), and embryonic development Involves G protein and GTP 1. G protein (cytoplasmic side) is off when bound to GDP 2. Ligand binds to extracellular side of receptor 3. Receptor is actived (shape) and binds to G protein 4. GTP replaces GDP on G protein 5. G protein binds to and activates an enzyme 6. G protein hydrolyzes GTP to GDP (GTPase) and returns to start Receptor Tyrosine Kinases kinases transfer phosphate groups Involved with enzymatic activity Ex. Growth hormone binding/response 1. Individual receptor tyrosine kinase proteins bind a signaling molecule (ligand) 2. Tyrosine kinase proteins form a dimer 3. This activates the kinase region of each, and each tyrosine kinase phosphorylates its tyrosines via ATP 4. Once activated, it is recognized by relay proteins in cell and binds them 5. Often activates multiple pathways Ion Channel Receptors Involves gated responses involving ion flow Ex) neurotransmitters (ligands) and neurons(action potentials) Ions flowing across membranes create currents 1. Ligand binds to channel receptor while receptor is in closed conformation 2. Receptor changes shape to open gate 3. Very specific ion(s) begin to flow down their electrochemical gradient 4. This flow of ions affects cell function 5. Ligand dissociates, ending the process Intracellular receptor model Results in gene expression (ex. Testosterone effects) 1. Steroid hormone passes through plasma membrane and binds to receptor protein in cytoplasm 2. Activated receptor protein enters the nucleus and acts as a transcription factor for a particular gene