Cell Signaling Flashcards
reasons for cell signaling
cell-cell communication, responding to external conditions (signal like salt or heat), responding to internal conditions
4 steps of cell signaling
- synthesis/release/transport of signaling molecule to target cell
- recognition of signal by a receptor protein on or in target cell
- relay, amplification, integration, distribution and modulation of the signal inside target cell (signaling cascade)
- execution of cellular response by target proteins
step 2
number of different receptors is greater than the number of signals therefore the same signaling molecule can often act on more than 1 receptor
step 3- signaling cascades
are comprised of proteins and small molecule “second messengers” to relay, amplify, distribute and modulate the signal, usually involve both activation and inhibition
signaling cascade proteins
many act as molecular switches that activate or deactivate, phosphoproteins; G-proteins (GTPases)
signaling cascade small molecules
ex) cyclic AMP or Ca++ that are generated/released in large amounts in response to an activated receptor and act to quickly and “loudly” broadcast the signal to other parts of the cell
enzyme-coupled receptors
cell-surface receptor proteins, for example, RTKs (receptor tyrosine kinases)
signaling through receptor tyrosine kinases
- signal molecules bind to RTKs
- dimerization of receptor
- activation of intracellular kinase domains
- cross-phosphorylation at multiple tyrosine residues
- recruitment and activation of signaling proteins after phosphorylation (most RTKs induce activation of Ras protein)
Ras protein
G-protein, Ras-GTP activates a MAP kinase cascade that leads to intracellular signaling and changes in gene expression
G-protein coupled receptors
detect photons, odorants, neurotransmitters, hormones, peptides; ability to respond to neurological chemicals such as serotonin and hormones like adrenaline; 7-pass transmembrane receptors bound to G-protein, when bound to signal molecule GPCR changes conformation and binds to heterotrimeric G-protein, binding of GPCR to this alpha site causes a conformational change that triggers release of GDP (activated GPCR functions as GEF), now-activated alpha and beta+gamma subunits separate and cause downstream effects
phosphoproteins
change activity or localization of a signal and are modified by phosphorylation (kinase and phosphatase), can be either on or off in either state
G-proteins
GTPases, on when bound to GTP and off when bound to GDP, GTP to GDP (GTP hydrolysis) is regulated by GAPs (GTPase activating protein) and GDP to GTP by GEFs (guanine nucleotide exchange factor); heterotrimeric with 3 parts (alpha, beta, gamma), alpha bound to GTP or GDP
ion-channel-coupled receptors
gated ion channels, respond to a variety of stimuli, mechanically gated, ligand gated and voltage gated
voltage gated ion channel receptors
difference in potential energy because of ion concentrations inside and outside target cell, change in voltage leads to conformational change, ex) neurons function through signal transduction through ion channels, ions change voltage of target cell sending a signal, entry of positive ions into a neuron makes neuron more likely to send a signal to other neurons
ligand gated ion channel receptors
intracellular/extracellular ligand, ligand binds and leads to conformational change, ex) neurotransmitter binding leads to conformational change that creates a pore for sodium ions to enter the neuron: then entry of sodium makes neuron slightly more positive and this voltage change can alter voltage-gated ion channels
