cell signalling Flashcards
what is cell signalling?
cell signalling is the process by which cells communicate with one another.
what are the 3 stages of cell signalling?
- signal reception
- signal transduction
- cellular response
define and describe signal reception.
signal reception refers to the target cell’s detection of an extracellular signal molecule.
- a signal is detected when a signal molecule (ligand) binds to a specific receptor protein located at the cell’s surface or inside the target cell.
- ligand-receptor interaction is highly specific -> a ligand binds to a specific complementary site on the target cell’s receptor to form a ligand-receptor complex. this causes the receptor protein to undergo a conformation change (which for usually activates the receptor)
there are 2 types of signal receptor proteins - intracellular (not in syllabus) and extracellular/cell surface/membrane receptors
define and describe signal transduction.
signal transduction is the process by which a target cell converts an extracellular signal into an intracellular signal that results in a specific cellular response
- the formation of the activated ligand-receptor complex changes the conformation of the receptor protein, initiating transduction
- transduction sometimes occurs in a single step (for signalling mediated by intracellular receptors). but usually, for cell surface membrane receptors, transduction occurs in a multistep signal transduction pathway consisting of a series of relay molecules
- the relay molecules are usually enzymes that operate in a specific sequence; each protein in the pathway typically acts by altering the conformation of and activating/inhibiting the protein immediately downstream. conformational changes are usually brought about by phosphorylation, creating a phosphorylation cascade
- transduction may also involves non-protein second messengers that relay the signal from the cell surface into the cell interior through diffusion
describe cellular response.
- a signal transduction pathway eventually leads to the regulation of one or more cellular activities
- a response may occur in the cytoplasm (cytoplasmic response) or may involve action in the nucleus (nuclear response)
- cytoplasmic response mainly changes cell metabolism
- nuclear response involves changes in gene expression, such as turning specific genes on or off in the nucleus
why are membrane receptors hydrophilic?
the receptors are hydrophilic and are unable to diffuse across the hydrophobic core of the cell membrane,
allowing them to bind to specific sites on cell surface receptor proteins.
what are the 4 main types of cell surface receptors?
- G-protein linked receptors (GPLR)
- receptor tyrosine kinases (RTK)
- ion channel receptors (FYI)
- integrin receptors (FYI)
what is phosphorylation?
phosphorylation is the process by which a protein kinase (PK) transfers phosphate groups from ATP to a protein.
PK phosphorylates and activates (downstream) protein kinases, turning on the signal transduction pathway
phosphorylation does not always lead to activation of a protein
the signal is transmitted by a cascade of sequential protein phosphorylation, each bringing with it a conformational change. this changes a protein from an inactive form to an active form
what is dephosphorylation?
dephosphorylation is the process by which a protein phosphatase (PP) removes phosphate groups from proteins
PP dephosphorylates and thus inactivates protein kinases, turning off the signal transduction pathway when the initial signal is no longer present -> protein kinases are available for reuse
what are second messengers and what do they do?
second messengers are non-protein signal molecules (include small, non-protein, water soluble molecules/ions)
second messengers transmit the message carried by the first messenger into the target cell’s interior.
- binding of first messenger onto receptors stimulates an increase in conc of second messengers
- small & water soluble second messengers can readily spread throughout the cytosol by diffusion
- binding of second messengers to relay proteins alter the latter’s behaviour
- second messengers enable cells to mount a large-scale, coordinated response following stimulation by a single extracellular signal molecule
describe the structure of g-protein linked receptors (GPLR)
primary structure - each GPLR protein is made up of 1 polypeptide chain
secondary structure - the single polypeptide chain comprises of 7 α-helices spanning the cell membrane, connected by non-helical segments
tertiary structure - hydrophobic interactions between the 7 transmembrane α-helices result in a barrel shape conformation. hydrogen bonds and a highly conserved disulfide linkage between the non-helical segments also stabilise the protein.
the N terminus and 3 non-helical segments form the extracellular domain of GPLR. the seven α-helices form the membrane-embedded domain. the C-terminus and 3 other non-helical segments form the intracellular domain. GPLR has different binding sites for the specific signal molecule and G protein
how do the properties of GPLR amino acid residues aid their function?
GPLR a.a. residues that form the inter-helical loops and N&C termini are hydrophilic - enables extracellular & intracellular domains to be soluble in aqueous mediums and also interact with water-soluble ligands (outside) and G-protein (inside)
hydrophobic GPLR a.a. residues are primarily found in the 7 transmembrane α-helices - enables the membrane-embedded domain to be stabilised and embedded within the membrane bilayer.
how does the structure of binding/interaction site of GPLR relate to its function?
extracellular domain contains specific a.a. at signal-binding site - enables signal-binding site to have specific 3D conformation that allows for interaction with specific ligand, resulting in a huge diversity of ligands that different GPLRs can bind to.
intracellular domain contains specific a.a. at G-protein interaction site - enables G-protein interaction site to have specific 3D conformation to bind and activate G-protein
binding of ligand to GPLR causes a conformational change in protein, allowing it to interact with G-protein -> enables GPLR to initiate signal transduction pathways via activation of G-protein
describe how signalling is mediated by a GPLR in response to signal molecule binding.
- the signal molecule binds to the extracellular side of the GPLR and causes a change in receptor conformation, activating the GPLR
- with an increased affinity for the G protein, the cytoplasmic side of the GPLR binds an inactive G protein, causing a GTP to displace the GDP bound to the G protein. this activates the G protein
- the activated G protein dissociates from the GPLR and diffuses along the membrane,
- the activated G protein binds to a target protein, usually an enzyme, altering target protein activity
- a change in target protein (enzyme) activity initiates a cascade of signal transduction events by triggering the next step in the transduction pathway inside the cell, including the production of cyclic AMP OR IP3 and release of Ca2+ (these 3 serve as 2nd messengers)
- the last activated molecule in the transduction pathway triggers a cellular response.
- the intrinsic GTPase activity of the G protein soon hydrolyses its bound GTP to GDP, so that the G protein is inactive again, the signal molecule has also dissociated from the GPLR
- the inactive G protein leaves the enzyme, which returns to its original inactive state. the G protein is now available for reuse
what does adenylyl cyclase do?
adenylyl cyclase converts ATP to cAMP in response to an extracellular signal molecule that binds to GPLR