Lecture 14 - Activation and Inhibition of Proteins Pt. II Flashcards
What are some ways that a message can be passed on during signal transduction?
- Proteins
- Chemical signals (second messengers)
- Sequential phosphorylation
What do the multi-step pathways of signal transduction help provide?
opportunities for coordination and regulation of the cellular response
Which of the two mechanisms of signal transduction are most common to many receptors?
second messengers, and phosphorylation
What receptors use second messengers?
many different receptors, especially GPCRs
What are second messengers?
intracellular molecules that change in concentration in response to receptor activation
How do second messengers work?
transmit signals form the receptor to other relay molecules because they are not attached to the membrane
What does Phosphorylation and Dephosphorylation do to proteins?
Turn protein activity on and off, or up and down
How does phosphorylation occur?
Protein kinases transfer phosphates from ATP to protein
How does a phosphorylation cascade occur?
Via the use of many different protein kinases
How does dephosphorylation work?
Protein phosphatases rapidly remove the phosphates from proteins to carefully control signal transduction
What are some ways that signal transduction is tightly regulated?
- Ligand dissociation
- Internalisation (removal of receptor from cell surface via endocytosis)
- Phosphatases
How does signal transduction occur in GPCRs?
- GPCRs use G proteins to start signal transduction
- GPCR activates the G protein which communicates with other proteins in the cell
- Different types of G proteins cause different effects
What are some examples of G proteins?
How does Glucagon (A peptide ligand) receptor signal transduction occur?
- Glucagon receptor is a GPCR
- Glucagon binds receptor
- Receptor activation causes G Protein activation + leads to further signal transduction events
- Leads to Glycogen breakdown + lipolysis
How does GLP-1 receptor signal transduction occur?
- GLP-1 receptor is a GPCR
- GLP-1 binds receptor
- Receptor activation causes G protein activation and further signal transduction
- Leads to insulin secretion
What is GLP-1?
A peptide ligand that is produced in the gut, and acts on pancreatic Beta-cells
How are adaptor proteins phosphorylated? (starts signal transduction in RTKS)
- agonist ligand binds
- receptor changes conformation and becomes activated
- receptor autophosphorylation occurs
- adaptor protein is phosphorylated
How does signal transduction occur in RTKs?
- Agonist ligand binds
- Adaptor protein is phosphorylated
- Adaptor proteins communicate with other proteins in the cell
- Different types of adaptor protein result in different effects
How does insulin receptor signal transduction in muscle and adipose cells occur?
- Insulin binds to insulin receptor (an RTK)
- Receptor activation causes phosphorylation of adaptor protein + further signal transduction events
- Leads to GLUT-4 translocation
- Permits entry of glucose into cell
What is insulin?
An endogenous peptide ligand
How does insulin receptor signal transduction in liver cells occur?
In liver cells, receptor activation causes phosphorylation of an adaptor protein and further signal transduction events. However this leads to Glycogen synthesis in the liver rather than glucose entry
How do ligand gated ion channels differ from other receptor classes?
- Instead of the use of relay proteins like G proteins or adaptors being used ions directly flow through the channels to produce effects
- Faster signalling compared to GPCRs and RTKs
How are ligand gated ion channels activated?
Binding of an agonist ligand causes a conformational change to activate receptor
How can cellular responses be controlled by receptors?
Depending on where receptors are expressed
Why can different cells detect and respond differently to the same ligand?
Because they have different collections of receptor and relay molecules
How can the same ligand and receptor pairing result in different effects in different cells?
different cells use different combination of relay molecules for signal transduction
What is the role of the pathway branching and ‘cross-talk’ in cellular signalling?
Helping coordinate signals from incoming ligands
