Cell Signalling Flashcards
What is paracrine signalling?
A signalling cell secretes a ligand and this works locally on another cell which expresses the cell surface receptor
What is autocrine signalling?
A signalling cell secretes a ligand, but the cell which secreted it expresses the receptor and therefore it works on itself
What is endocrine signalling?
An endocrine cell secretes a hormone -> enters the blood stream -> delivered to the target cell which expresses the receptor
Give an example of endocrine signalling
Insulin is produced -> enters the blood -> has to reach target tissues which are far away including skeletal muscle, liver and adipose tissue
What is synaptic signalling?
The neuronal cell body secretes a neurotransmitter in a vesicle into the synapse -> binds to the cognate receptors on the target cell
What is contact dependent signalling?
The signalling molecule contains a membrane-bound signal molecule and therefore the target cell has to be in close proximity to be activated
What is matrix dependent signalling?
The tissue above induce inflammation to be passed from the basement membrane to the focal membranes and hemidesmosomes
What is gap junction signalling?
Direct cell to cell contact through gap junctions to transmit a signal
What are the 4 forms of signal transduction?
Conformational-coupling (preformed complex)
Conformational-coupling (diffusion-dependent complex formation)
Posttranslational modification
Protein degradation
What is conformational-coupling (preformed complex)?
the proteins are directly coupled to one another
What is conformational-coupling (diffusion-dependent complex formation)?
The two proteins are far apart and therefore have to diffuse to be brought together so they can bind
What is posttranslational modification?
One protein activates another through posttranslational modifications
What is protein degradation?
The proteins are bound together normally and degradation of one results in activation of the other
What are protein:protein interactions?
Where one protein binding to another induces a response
What is macromolecular complexes?
Involves a scaffold
The proteins bind to the scaffold is a specific order so they can only interact with the one specific protein
What are protein modules?
Domains which bind to a specific phosphorylated residue on a target protein
Name 6 examples of protein modules
SH2 PTB 14-3-3 Sh3 PDZ WW
What does SH2 recognise?
Phosphotyrosine motif
What does PTB domain recognise?
Phosphotyrosine motif (different sequence to SH2)
What does 14-3-3 recognise?
Phosphorylated serine residues
What does SH3 recognise?
Proline rich regions
What is the MAPK signalling pathway?
EGF -> EGFR phosphorylation -> SHC -> GRB2 -> SOS -> Ras -> Raf -> MEK -> ERK -> Myc, Ap1, ETS and EGR1
What 5 ways can a target cell become desensitised to a signalling molecule
Receptor sequestration Receptor downregulation Receptor inactivation Inactivation of signalling protein Production of inhibitory protein
What is receptor sequestration?
The signalling molecule binds to receptor -> internalised as an endosome -> receptor translocates back to the membrane and the ligand is degraded
What is receptor downregulation?
The receptor is internalised along with the ligand -> both degraded in the lysosome
What is receptor inactivation?
A protein binds to the cytoplasmic region of the receptor and inhibits it
What is inactivation of signalling protein?
A protein binds to the downstream target of the receptor and inhibits it
What is production of an inhibitory protein?
A downstream protein is produced which inhibits one of the proteins upstream
Cancers associated with the MAPK signalling pathway
Hypermutated CRC Non-hypermutated CRC Melanoma Glioblastoma Pancreatic adenocarcinoma Lung adrenocarcinoma
Types of mutations in EGFR?
Receptor amplification
Mutations on the extracellular region so it thinks it is seeing a ligand when it is not, making it constitutively active
Mutations in the intracellular domain of the receptor making it constitutively active
