Activation and inhibition of proteins #2 Flashcards
Signal transduction process
Active receptor starts a chain of events -> messages passed on through cell via signal transduction
Often multi-step pathways, provide opportunity for coordination and regulation
Message can be passed on using proteins, second messengers or phosphorylation
What are second messengers?
Many different receptor especially G protein coupled receptors use second messengers. They can transmit from a receptor to other relay molecules as they’re not attached to the membrane (free to move in cell)
What is Phosphorylation?
Phosphorylation is a widespread mechanism for regulating protein activity where protein kinases transfer phosphates from ATP to protein
What is dephosphorylation?
Dephosphorylation is when protein phosphates rapidly remove phosphates from proteins to carefully control signal transduction (often use many different protein kinases -> creates phosphorylation cascade)
Examples of mechanism using signal transduction
- Ligand dissociation (makes receptor inactivated)
- Internalisation - receptor removed from cell surface through endocytosis (once activated) so it can no longer respond to ligand
- Phosphatase’s
What is the function of GPCR?
The GPCR activates the G protein (relay protein in cascade) which communicates with other proteins in cell. There are different types of G proteins which have different effects on signalling
Gas= stimulators G protein which activates an enzyme called adenylate cyclase
Gai= inhibitory G protein, decreases the activity of adenylate cyclase
What is the G protein?
Guanine nucleotide binding protein. They’re heterotrimeric meaning they have 3 different subunits - alpha, beta and gamma - inactivated in the G protein cycle where GTPl and GDP exchange
Glucagon receptor example - GPCR
Glucagon binds to receptor, receptor activation causes G protein activation and further signal transduction events leading to glycogen breakdown
GLP-1 receptor example - GPCR
GLP-1 binds to receptor, receptor activation causes G protein activation and further signal transduction events, glycogen breakdown, leading to insulin secretion
Receptor tyrosine kinase - signal transduction
Phosphorylation: agonist ligand binds -> receptor changes conformation/shape and becomes activated -> receptor autophosphorylation occurs -> adaptor protein is phosphorylated and passes on signal. Adaptor proteins communicate with other proteins in cell, different adaptors = different effects
Insulin receptor example - RTKs
Receptor activation causes phosphorylation of an adaptor protein and further signal transduction events, leading to GLUT-4 translocation. In liver cells receptor activation causes phosphorylation, causing signal transduction events, leading to glycogen synthesis
Ligand-gated ion channels
Slightly different to other receptors. An agonist ligand that binds causes a conformational/shape change to activate the receptor, however, instead of relay proteins, ions directly flow through channel to produce effects. Receptors produce faster signalling (ionotropic) in comparison to GPCR and RTK (metabotropic)
Other points about signal transduction
Responses can be controlled by where receptors are expressed. The same ligand/receptor pairing can have different effects leading to unique responses. Pathway branching and cross-talk further help the cell coordinate signals from incoming ligands
Adenylate cyclase - GPCR
Agonist ligand causes GPCR to bind to Gas which actives the simulating protein, adenylate cyclase, which produces cAMP (a second messenger) which is free to diffuse into the cell and activates Protein kinase A (PKA) leading to further signal transduction -> cell response
