Signaling Flashcards
Signal
Leads to changes in protein production. Integrate signals to generate diverse set of outputs: survive, grow and divide, differentiate, or die.
Ligand
A molecule that binds to receptor. Can be secreted proteins, membrane proteins, hormones, ions, chemicals, pressure, heat, light, or even vibrations.
Receptor
Proteins that receive and transduce signals.
Relay Molecules
Intracellular signaling proteins or second messengers.
Switches
Signaling by phosphorylation (conformation change) or GTP binding (ATP is very common, GTP is less noisy and common)
Scaffolds/Adaptors
Scaffolds increase the speed and specificity of signaling by acting as platforms, usually with discrete binding sites that associate (often stably) with specific proteins in order to create a complex. Adaptor proteins contain protein-binding motifs, which facilitate interactions between protein-binding partners in the context of bigger signaling complexes.
Juxtacrine
Contact-dependent. Can signal in both directions, but have to touch each other. Membrane bound signal molecule binds receptor .
Autocrine
Self-signaling. Secrete signal and responds to itself.
Endocrine
Long range. Signals, like hormones, go into bloodstream until the bind receptor in target cell.
Ion-channel Couples Receptors
Cell Surface Receptor 1. Sit in membrane and wait for ions to change conformation. They then open or close because signal binding opens “gate” so ions can pass through the channel. Channel pores can be electrically coupled (voltage-gated). They can serve as pumps, for example pumping to pull calcium back into sarcoplasmic reticulum.
G-Protein Coupled Receptors (GPCRs) - trimeric G proteins as opposed to the small GTPase proteins we’ve discussed.
Cell Surface Receptor 2. 7-pass transmembrane protein where signal binding induces GTP-binding protein binding and activation. Active G-protein goes on to activate downstream proteins. Can respond to light, sounds, chemicals, smell, taste, neurotransmitters, hormones.
Enzyme coupled receptors
Cell Surface Receptor 3. Signal molecule activates enzymatic activity directly or indirectly. Enzymatic activity can be phosphorylation, ubiquitination, GTP exchange, or hydrolysis. Most developmental signaling pathways are like this. Signal molecule in form of dimer could activate catalytic domain by bringing two together to activate itself.
Phosphorylation
Ativates
Protein Kinase
Adds phosphate group by using ATP.
Protein Phosphatase
Removes phosphate group.
Phosphorylation
Conformation change. Can work both ways, phosphorylation can inhibit function /de-phosphorylation can activate function.
Positive Feedback
Stimulus turns on A which turns on B which turns on A.
Negative Feedback
Stimulus turns on A which turns on B which tells A to stop.
Chemoattractant
Chemical signal that attracts/directs cell movement.
Rac
Rho family GTPase. Activation of Rac promotes actin polymerization (via arp2/3) at the cell periphery, leading to the formation of sheetlike lamellipodial extensions (Flattened, sheetlike protrusion supported by a meshwork of actin filaments, which is extended at the leading edge of a crawling animal cell). Tips balance towards branched actin web networks and away from stress fiber formation.
Rho
Rho family GTPase. Activation of Rho promotes both the bundling of actin filaments (via formins) with myosin II filaments into stress fibers.
Cdc42
Rho family GTPase. Activation of Cdc42 on the inner surface of the plasma membrane triggers actin polymerization and bundling to form filopodia (Thin, spike-like protrusion with an actin filament core, generated on the leading edge of a crawling animal cell). Activation of Cdc42 increases actin nucleation via wASP stabilization which enables it to bind arp2/3.
WASP
Activates Arp2/3
Notch/Delta
Notch receptors are themselves such proteins, which are activated by cleavage when Delta on another cell binds to them; the cleaved cytosolic tail of Notch migrates into the nucleus, where it stimulates the transcription of Notch- responsive genes.
RNA in situ Hybridization
Measure transcriptional activity of a pathway. Make RNA complimentary to specific mRNA. This RNA has labeled Uridine so that antibody can bind. U is used because it’s specific for RNA. Then, add phosphatase so that when colorless compound is added, it becomes purple when the phosphatase removes the phosphate.
Reporter Gene
Measure transcriptional activity of a pathway. Fuse lacZ or GFP to enhancer/promoter to see where promoter for gene of interest is being transcribed.
