The affinity to strongly bind to a ligand may also change Receptors can be blocked Receptors that are blocked by a small molecule or drug cannot receive the signal Lipid soluble vs. Lipid insoluble signals Ability of a signaling molecule to pass through lipid bilayers is crucial in determining how a target cell recognizes it Most lipid soluble signaling molecules can diffuse across the hydrophobic region of the plasma membrane and enter the cytoplasm of target cells Large or hydrophilic signaling molecules cannot cross the plasma membrane They must be recognized at the cell surface Clicker Question #3: In “Signal Reception,” A single receptor is present, the signal receptor can be blocked by a small molecule, and the signal molecule can be either hydrophobic or hydrophilic Step 2: Signal Processing Once a cell receives a signal, something must happen to initiate the cell’s response Lipid soluble molecules can be directly processed without any intermediate steps Lipid insoluble signals must undergo signal transduction Conversion of a signal from one for to another The extracellular signal is converted into an intracellular signal, and is usually amplified
Clicker Question #4: Signal Transduction and Signal Amplification occur for Lipid insoluble signals Signal Transduction Signal transduction begins at the plasma membrane Amplification occurs inside the cell Two major types of signal transduction and amplification systems: G-protein coupled receptors initiate production of intracellular “second messengers” that then amplify the signal Enzyme-linked receptors trigger protein activation in the cell (ex. Phosphorylation) G-protein coupled receptors In response to ligand binding, the receptor changes shape and activates its G-protein The active G-protein interacts with another protein in the plasma membrane This produces a second messenger Second messengers Second messengers are small, non-protein signaling molecules that elicit an intracellular response to the first messenger They are not restricted to a single role or cell type More than one second messenger may be triggered by the same extracellular signaling molecule
Enzyme-linked receptors Signal reception causes receptors to dimerize The activated receptor complex phosphorylates itself at tyrosine residues Binding proteins bind to the receptor, and one activates Ras by exchanging GDP for GTP Activated Ras activates a protein kinase A phosphorylation cascade results, and causes some effect in the cell Step 3: Signal Response Second messengers or kinase cascades ultimately alter gene expression or activate/deactivate proteins in the target cell Crosstalk Signal transduction pathways form a network, so cells may respond to many signals in an integrated manner Clicker Question #5: Signal Transduction do not always act independent of each other
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