Activation and Inhibition of Proteins #2 Flashcards
Describe signal transduction
- Active receptor starts a chain of events where messaged are passed on through the cell bia a process called signal transduction (this is a broad term for many aspects of cellular communication)
- These are often multi-step pathways that provide opportunities for coordination and regulation of the cellular response
- The message can be passed on using proteins, chemical signals called second messengers or through sequential phosphorylation
What are the two main mechanisms of signal transduction?
Second messengers and phosphorylation
Describe second messangers
- Many different receptors, especially G-protein coupled receptors use second messengers
- These are intercellular molecules that change in concentration in response to receptor activation and transmit signals from the receptor to other relay molecules because they are not attached to the membrane
Describe phosphorylation and dephosphorylation events
These events turn protein activity on or off or up or down as required.
- Widespread mechanism for regulating protein activity where protein kinases transfer phosphates from ATP to protein (phosphorylation)
- Protein phosphatases rapidly remove the phosphates from proteins (dephosphorylation) to carefully control signal transduction
- Signal transduction pathways often use many different protein kinases, creating a phosphorylation cascade.
List three ways that signal transduction is highly regulated to control cellular activity
- Ligand dissosciation - when it can bind to the receptor and then unbind from it
- Internalisation - receptor is removed from the cell surface through endocytosis so it can no longer respond to ligand
- Phosphatases
Describe signal transduction for GPCRs
- G protein-coupled receptors (GPCRs) use G proteins to start signal transduction, hence their name
- The GPCR activated the G protein, which communicates with another protein in the cell
- There are different types of G proteins, which have different effects
G-alpha-s: stimulatory G protein, which activates an enzyme called adenylate cyclase
G-alpha-i: inhibitory G protein, decrease the activity of adenylate cyclase
Describe the pathway of signal transduction for a Gs-coupled GPCR
- agonist ligand binds
- receptor activates the stimulatory G protein
- which activates the adenylate cyclase
- resulting in production of cAMP (a second messenger)
- which activates kinase
- further signal transduction leading to a cellular response
Give two examples of GPCR
Glucagon receptor signal transduction:
- Glucagon (agonist - and an example of a peptide ligand) binds to GPCR
- receptor activation causes G protein activation and further signal transduction events, leading to glycogen breakdown
- glucagon receptro signal transduction also contributes to lipolysis
GLP-1 receptor signal transduction:
- GLP-1 produced in the gut and acts on pancreatic beta cells
- GLP-1 (peptide ligand) binds to GPCR
- receptor activation causes G protein activation and further signal transduction events, leading to insulin secretion
Describe signal transduction for RTKs
- Receptor tyrosine-kinases (RTKs) use phosphorylation of so-called adaptor proteins to start signal transduction
- agents ligand binds > receptor changes conformation and becomes activated > receptor autophosphorylation occurs > adaptor protein is phosphorylated
- Adaptor proteins communicate with other proteins in the cell
- There are different types of adaptor protein, which have different effects
Provide specific RTK examples
Insulin receptor signal transduction (i):
- Insulin binds receptor
- receptor activation causes phosphorylation of an ‘adaptor’ protein, and further signal transduction events, leading to GLUT-4 translocation
Insulin receptor signal transduction (ii):
- insulin binds to receptor
- in liver cells, receptor activation causes phosphorylation f an ‘adaptor’ protein and further signal transduction events, this time leading to glycogen synthesis
This is an example of the same receptor for the same ligand producing slightly different cellular responses.
Describe signal transduction for ligand-gated ion channels
- Ligand-gated ion channels are slightly different to other receptors
- An agonist legal that binds causes a conformational change to activate the receptor
BUT - Instead of ‘relay’ proteins like G proteins or adaptors being used, ions directly flow through the channel to produce effects
- these receptors produce fast signalling compared to the slower signalling of GPCRs and RTKs
Describe a few more important points about signal transduction
- Responses can be controlled by where receptors are expressed
- Different cells have different collections of receptors and relay molecules, allowing cells to detect and respond differently to different ligands
- The same ligand/receptor pairing can have different effects in different cells because they use different combinations of relay molecules for signal transduction
- Pathway branching and ‘cross talk’ further help the cell coordinate signals from incoming ligands
