Molecules in the Signaling Cascade PDF

MODULE 26 Molecules in the Signaling Cascade Relay Proteins: Pass the message to the next signaling component. Messenger Proteins: Carry the signal from one part of the cell to another. Adaptor Proteins: Link one signaling protein to another. Amplifier Proteins: Enzymes or ion chann...

MODULE 26 Molecules in the Signaling Cascade Relay Proteins: Pass the message to the next signaling component. Messenger Proteins: Carry the signal from one part of the cell to another. Adaptor Proteins: Link one signaling protein to another. Amplifier Proteins: Enzymes or ion channels that increase the signal by producing many intracellular mediators or activating many downstream proteins. Transducer Proteins: Convert the signal into a different form. Integrator Proteins: Receive signals from two or more pathways and integrate them before relaying the signal onward. Latent Gene Regulatory Proteins: Activated at the cell surface and migrate to the nucleus to stimulate gene transcription. Scaffold Proteins: Organize groups of interacting signaling proteins into complexes. Molecular Switches in Signaling molecular switch is a molecule that switches from an inactive to an active state until a process/signal switches it off proteins are phosphorylated and dephosphorylated by a kinase and phosphatase, respectively; the serine/threonine kinases are the most common types of protein kinases kinase cascade is a chain with several kinases, each activated by phosphorylation and then phosphorylating the next kinase GTP-binding proteins switch to an active state when GTP is bound and an inactive state when GDP is bound the phosphorylated state is not always the active state phosphorylation occurs only at specific Tyr, Thr, and Ser residues, depending upon the context (histidine is not phosphorylated in animals) MODULE 26 More on the Phosphorylation/Dephosphorylation Switch phosphorylation/dephosphorylation is the most common switch mechanism it is rapid compared to allosteric binding, it is more universal: tyrosine, serine, and threonine residues are in all proteins, whereas allosteric modulators have to be unique for each protein unlike serine/threonine phosphatases, tyrosine phosphatases remove phosphate groups from selected phosphotyrosines phosphorylation can induce a protein conformational change or provide a docking site for a protein Nuclear Receptors Retinoids, steroid, and thyroid hormones: small, hydrophobic, diffusing across the plasma membrane; soluble for transport in the blood by carrier proteins. Activated receptors bind to DNA to regulate gene transcription. Some nuclear receptors are activated by intracellular metabolites, not by secreted signals. Some receptors are in the cytosol and enter the nucleus after ligand binding. Thyroid and retinoid receptors are bound to DNA even in the absence of ligand; ligand binding alters the receptor conformation, causing a pre-existing inhibitory complex to dissociate. Putting It All Together Depending on the distance at which a ligand operates, signaling can be paracrine, endocrine, contact- dependent, or synaptic. Autocrine signaling is rare. Some signal molecules pass through the plasma membrane to activate intracellular receptors, which regulate the transcription of specific genes. Most extracellular ligands are hydrophilic and activate receptors on the cell surface. These receptors then relay the extracellular signal into intracellular pathways. There are three main families of cell-surface receptors: ion-channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors. Both enzyme-linked and G-protein-linked receptors pass signals through networks of intracellular proteins. Some signaling proteins act as molecular switches, becoming transiently activated by phosphorylation/dephosphorylation or GTP binding.