Overview
This section explains how ligand binding initiates signal transduction in cells, emphasizing phosphorylation, signaling cascades, and the role of second messengers in cellular responses.
Signal Transduction Initiation
- Signal transduction begins when a ligand binds to a cell-surface receptor, triggering conformational changes in the receptor.
- Only internal receptors can directly interact with DNA to initiate protein synthesis; cell-surface receptors transmit signals into the cytoplasm.
- Ligand binding can cause dimerization, where two receptors join to form a dimer and activate each other’s intracellular domains.
Signaling Pathways and Cascades
- Activation of the receptor sets off a signaling pathway—a chain reaction of protein and enzyme activations called a signaling cascade.
- Signaling cascades involve upstream (earlier) and downstream (later) events, leading to cellular responses such as metabolism changes or gene expression.
- Pathways can branch and integrate, allowing complex cell responses depending on protein expression and other signals.
- Signal amplification occurs when one ligand-bound receptor activates many downstream molecules.
Phosphorylation in Signal Transmission
- Phosphorylation involves adding a phosphate group (PO₄³⁻) to proteins, usually on serine, threonine, or tyrosine residues.
- Kinase enzymes catalyze phosphorylation, which can activate or inactivate target enzymes.
- Dephosphorylation, done by phosphatases, reverses the effect of phosphorylation.
Second Messengers
- Second messengers are small molecules that spread the signal after receptor activation.
- Calcium ion (Ca²⁺) acts as a second messenger by increasing in cytoplasm, leading to various cellular responses depending on the cell type.
- Cyclic AMP (cAMP), synthesized by adenylyl cyclase from ATP, activates A-kinase, which phosphorylates specific target proteins.
- Inositol phospholipids in membranes can be converted to second messengers like IP₃ and DAG by phospholipase C.
- DAG activates protein kinase C (PKC) and IP₃ triggers Ca²⁺ release from the endoplasmic reticulum, continuing the cascade.
Key Terms & Definitions
- Signal transduction — the process of transmitting a signal from outside to inside the cell after ligand binding.
- Dimerization — formation of a complex of two receptor molecules upon ligand binding.
- Phosphorylation — addition of a phosphate group to a molecule, often regulating protein activity.
- Kinase — enzyme that catalyzes phosphorylation.
- Phosphatase — enzyme that removes phosphate groups (dephosphorylation).
- Second messenger — small molecule that propagates a signal within the cell after receptor activation.
- cAMP — cyclic adenosine monophosphate, a common second messenger.
- DAG — diacylglycerol, a lipid-derived second messenger.
- IP₃ — inositol triphosphate, a second messenger that releases Ca²⁺ from internal stores.
Action Items / Next Steps
- Review the mechanisms of phosphorylation and second messenger function.
- Observe an animation of cell signaling (link provided in section).
- Be ready to discuss the effect of RAS G-protein inhibition on downstream signaling.