Intracellular Signalling Flashcards
Sensory Signalling (sensory receptors for…)
light, smell, taste, sound, balance, touch
Cellular environment (cells detect…)
nutrients, protons, osmotic pressure, xenobiotics
Signalling molecules (5 with examples)
- secrete into extracellular space (hormones, NTs)
- released through channels in PM (ATP)
- liberation of PM-embedded ligands (GF, cytokines)
- exposed but bound to surface (ephrins)
- extracellular matrix proteins (integrins)
6 Modes of Intracellular Signalling
Endocrine – release hormone into blood (insulin, PTH)
Paracrine – local mediators to nearby cells (PDGF)
Synaptic – neuronal communication (NTs)
Juxtacrine – physical contact, extruding ligand (ephrins)
Autocrine – acts back on own surface (IL-1, VEGF)
Protease-dependent – proteolytic activate of precursors
Affinity, Specificity, Saturability, Reversibility, Competition, Agonist, Antagonist
- tightly drug binds (high Kd = low affinity)
- ligands fits into pocket
- binding limited to #of receptors
- bind and dissociate
- compete with other ligands
- promoves activation
- does NOT activate receptor
3 ways cells respond to particular agonist
receptor expression level (availability of receptors)
receptor variants (distinct subtypes)
intracellular signalling components (interpret receptor signal)
Signal turnoff
deactivation (hydrolyze ACh or breakdown of hormones)
resorbed (uptake proteins)
mimicked agonists = metabolized or excreted
receptor activation to limit signalling
GTP Switch
activate vs deactivate = GTP bind + hydrolysis
GEF – promote GDP dissociation = active by GTP
GAP – promote GTP hydrolysis = deactivate G-proteins
GDI – inhibit GDP dissociation = no activation
Phosphorylation Switch
kinase = phosphorylate
phosphatase = de-phosphorylate
General Characteristics of Cell Signalling
1st messengers – receptor binds to agonist (intracellular signalling/concentration)
2nd messengers (IP3, DAG, cAMP) – alter target protein activity to change cell response
Signalling Cascade and Amplification
product of one step = activator/substrate of next step
- receptor reserve (less ligand needed to activate)
Strength of receptor signal depends on…
amplification
attenuation (limit signal)
scaffolding proteins (constituents close proximity)
desensitization (phosphorylate, less substrate, degrade)
Pleiotropy
one signal can elicit multiple outcomes
- GPCR —> activate alternate G proteins
Convergence
multiple signals activate common outcome
- RTK activate PI3K via p85
- GPCR activate PI3K via p101
Cell communication gone wrong
lose of signal (type I diabetes)
- pancreatic cells loss = loss of insulin signal
- treatment: add more ligand
target ignores signal (type II diabetes)
- target cells lose ability to respond = no receptor
- treatment: agonist to reduce glucose levels
