Cell Signalling Flashcards
biological role of signal transduction
Cells receive signals from the environment beyond the plasma membrane. Types of signals include: antigens, hormones, neurotransmitters, light, touch, pheromones
These signals cause changes in the cell’s composition and function, such as: differentiation and antibody production, growth in size or strength, cell division (proliferation), migration
receptors function
- interact with signals and translate message to cell
- Receptor: A membrane-bound or soluble protein or protein complex, which exerts a physiological effect after binding its natural ligand
typical ligands
Small ions - ferric ion: bacterial ferric receptor
Organic molecules - adrenalin: epinephrine receptor
Polysaccharides - heparin: fibroblast growth factor or ATIII
Peptides - insulin: insulin receptor
Proteins - vascular endothelial growth factor: VEGF receptor
six features of signal-transducing systems
a. Specificity
b. Amplification
c. Modularity
d. De-sensitization/Adaptation
e. Integration
f. Localized Response
receptors bind specific ligands
signal molecule fits binding site on its complementary receptor; other signals do not fit
Kd = dissociation constant – low Kd – high affinity
types of receptors (4 main)
- G protein−coupled receptors - epinephrine receptor
- Enzyme-linked receptors - insulin receptor
- Ligand-gated ion channels - nicotinic acetylcholine receptor
- Nuclear receptors - steroid receptors
- Other membrane receptors – integrin receptors
G protein-coupled signalling (GPC)
GPCRs are α-helical integral membrane proteins
- G proteins are membrane associated proteins that bind GTP
- G proteins mediate signal transduction FROM GPCRs TO other target proteins
example: Ras - oncogene protein, and adrenaline - interacts with cells via a GPCR
- stress response, mobilises E, induces liver cells to breakdown glycogen to release glucose
synthesis of cAMP
cAMP is a secondary messenger
- allosterically activates a variety of enzymes including cAMP-dependent protein kinase A (PKA)
- PKA activation leads to activation of enzymes that release glucose from glycogen
signal amplification cascade
eg in adrenaline
- activation of a few GPCRs leads to the activation of enzymes
- every enzyme makes several cAMP molecules
- therefore several PKA enzymes
- activates 1000s of glycogen degrading enzymes in liver
- therefore abundance of glucose released into bloodstream
desensitisation/adaptation
receptor activation triggers a feedback circuit that shuts off the receptor or removes it from cell surface.
eg down regulation of cAMP via hydrolysis of GTP in α subunit of G-protein
enzyme linked membrane receptors
consist of extracellular ligand-binding domain and intracellular catalytic domain
- most common catalytic domain has tyrosine kinase activity (adds phosphate group to itself, leads to conformational change allowing binding and catalytic phosphorylation of specific target proteins)
- eg insulin acts via a receptor tyrosine kinase
integration
when 2 signals have opposite effects on a metabolic characteristic - such as concentration of a second messenger - the regulatory outcome results from the integrated input from both receptors
modularity
proteins with multivalent affinities form diverse signalling complexes from interchangeable parts. phosphorylation provides reversible points of interaction
ligand-gated ion channels
regulates transport of ions across cell membranes
- respond to changes in membrane potential and ligand binding to specific receptor sites
- roles in NS inc: voltage-gated Na channels, nicotinic acetylcholine receptor, ionotropic glutamate receptor, gamma aminobutyric acid receptor A
membrane electrically polarised
inside of cell is negative charged compared with outside (~-50 to -70mV difference)
- membrane potential largely d/t asymmetric transport of Na+ and K+ via ATPase (for every 3 Na+ out, only 2 K+ in)
- flow of ionic species across the membrane depends on concentration gradient and overall electrical potential
example of voltage gated and ligand gated ion channels in nerve signalling
- nerve signals within nerve propagate as electrical impulses
- propagation of impulse involves opening of voltage-gated Na+ channels
- opening of voltage gated Ca2+ channels at end of axon triggers release of neurotransmitter acetylcholine
- acetylcholine opens the ligand-gated ion channel on the receiving cell
PROCESS example of voltage gated and ligand gated ion channels in nerve signalling
- depolarisation (Na+ channel open and Na+ flows in)
- repolarisation (K+ channel open and K+ flows out)
- voltage gated Ca2+ open triggering secretory versicles containing acetylcholine released
- acetylcholine crosses synaptic cleft to other cell, and
- binds to receptor ion channels on the cell
- Na and Ca flow into new cell causing action potential to propagate again
nuclear receptors
direct regulation of transcription by hormones
- hormone carried to target tissue on serum binding protein - diffuse across PM
- hormone bind to receptor in nucleus –> conformational change on receptor. forms diner with other hormone/receptor complexes. bind to hormones response elements on DNA
- hormone receptor complex attract other activators or repressors. lead to inc or dec in mRNA transcription
- altered levels of gene product translated –> cellular response
interns mediate cell adhesion
- extracellular domain interacts with AA containing ECM proteins - collagen, fibrinogen etc
- triggers cytoskeleton rearrangement and gene expression
- newly expressed genes bind to intracellular domain, triggering extracellular response –> proliferation and migration
