Topic 12 Cell Signalling

Extracellualr signal molecules

proteins (3D shapes), polypepetide (unfold/only function), amino acid, nucleotides, steroids, fatty acid derivatives (hydrocarbon chains)

Endocrine signalling

signals through blood stream, hormones produced by endocrine cells

Paracrine signaling

signal diffuse locally, through extraceullular fluid, local mediators

Autocrine signaling

respond to signal they produce, feedback to promote more/less production

Neuronal signaling

fast signal, specificity to 1 target cell, similar to paracrine

contact dependent signaling

direct contact , signal and receptor molecules in plasma membrane

Receptors

high selective, receive signal, activate intracellular signalling, activates effector proteins, surface or intracellular

Cell surface receptors

bind extraceullar signals, signal to large/hydrophilic to cross membrane

Intracellular receptors

bind signal in cell, signal small and hydrophobic to pass membrane

Cell response

occurs once signal received, fast or slow depending effect

Intracellular signaling pathways

relay of message across membrane (step 1), relay race between signal molecules, reaches effector protein/target molecule, amplify/distribute signal, regulated through feedback (pos - enhances/neg- diminshes), uses scaffold, not linear, interact and intergrate

Molecular switches

inactivation for every activation step, cascade of kinase phosphorylating followed by phosphatase dephosphorylating, GTP binding proteins

Type of kinases

Serine-threonine kinase, Tyrosine kinase

GTP binding proteins

on when GTP bound, shut themselves off by hydrolyzing (GTPase activity), must replace GDP to reactivate

Cell-surface receptors type

ion channel coupled, G protein coupled, Enzyme coupled

Ion channel coupled receptors

ligand gated channel, signal molecule open channel/changes permeability, changes membrane potential

G-protein coupled receptors

Activate GTP binding proteins, initiate intraceullar signaling cascade, single polypetide has 7 alpha helices through the membrane, function quickly (taste/smell/sight)

G protein

3 subunits (alpha,beta,gamma), alpha and gamme membrane bound(to lipid), alpha has GDP which replaced with GTP when activated, subunit break apart to relay signal, alphas has GTPase to hydrolyze GTP (back to inactive GDP)

G protein functions

target of bacterial toxins (cholera), control gated ion channels (pacemaker cells), activates enzyme that make small messengers (amplify and spread signal)

Adenylyl cyclase activiy

made from hydrolyzed ATP, activate cyclic AMP dependent protein kinase (PKA) to phosphorylate intracellular proteins

AMP phosphodiesterase

converts cAMP to AMP, prevents PKA pathway, caffeine blocks function

cell response to cyclic AMP dependent protein kinase (PKA)

increase heart rate, glycogen breakdown (synthesis stoped), Fat breakdown, cortisol secretion

Enzyme coupled receptors

enzyme or associate to activate intraceullar signal pathways, slow reposnes, changes in gene expression, have catalytic domain, dimers(2)

Receptor Tyrosine Kinase (RTKs)

enzyme coupled receptor, dimers kinase domains phosphorylate eachother, phosphorylated tyrosine serveas docking sites (interaction domain), signal proteins bind, transmit several routes, biomolecular condensates (adapter proteins), terminated by phosphatase or more commonly endocytosis/destruction