L41- Cell signalling (enzyme linked receptor) Flashcards
what is an enzyme-linked receptor?
- they possess an in-built receptor
- these enzymes are acivated upon ligand binding
what do enzyme-linked receptors do?
-They relay the extracellular signal to the nucleus by a sequence of interaction that eventually switch on specific transcription factors, altering gene expression in the cell
what are the different enzyme-linked receptor structure?
- ligan-binding domain
- transmembrane domain
- intracellular catalytic domain
what is the role of the Ligand-binding domain?
- Extracellular to allow easy access for ligands
- Strong affinity for specific ligands
what is the role of the transmembrane domain?
- Contains a series of hydrophobic amino acids
- Tethers the receptor to the cell membrane
what is the role of the intracellular catalytic domain?
-Either intrinsic to the receptor or tightly bound via
the cytosolic domain
-Majority are kinases
what is kinase?
-it is an enzyme that catalyses the transfer of a phosphate from ATP>to a specific protein.
what enzyme carries out phosphorylation?
kinase
what enzyme carries out dephosphorylation?
phosphatase
what are some downstream effects of kinase-linked receptors?
- cell growth
- apoptosis
- tissue repair
- immune response
explain 2 way of a signal-mediated response?
either:
-receptor is phosphorylated leading to the kinase then getting phosphorylated>TF
or
-When ligand attaches to the
name one type of major enzyme-linked receptor?
- Receptor tyrosine kinase (RTK)
- receptor serine/threonine kinase
- tyrosine kinase associated receptors
how does a receptor tyrosine kinase work?
- signal molecule will bind to signal binding site on receptor causing a conformational change
- this change will bring the 2 polypeptides together to form a dimer formation
- this activates the tyrosine kinase regions
- the kinase allows the tyrosine to be phosphorylated using ATP forming a phosphorylated dimer
- relay protein such as SH2 binds to the phosphotyrosine and conformational change leading to signal transductional pathway for cellular response.
What is Src homology 2 (SH2) domains?
they bind to phosphotyrosine residues, they are very specific
how many types of receptor serine/theronine kinase is there?
2: type I AND TYPE II
What is receptor serine/theronine kinase type I?
Inactive unless in complex with type II receptors
Do not interact with ligand dimers
Contain conserved sequences of serine and threonine residues near to their kinase domains
What is receptor serine/theronine kinase type II?
Constitutively active kinase domains (even in the absence of
the bound ligand).
Able to phosphorylate and activate the type I receptor.
how does a receptor sarin/threonine kinase work?
-type I is kept inactive by a portion of its cytosolic domain that blocks its kinase activity
-BMP ligands bind as dimers to type II receptor
type II receptors thenbind and phosphorylate type I receptor this removes the inhibition of type I kinase activity
-type I receptor then phosphorylate Smad transcription factors allowing it to enter the nucleus to repress or activate target gene expression.
what is the main ligand for tyrosine kinase associated receptors?
cytokines
what happens during a tyrosine kinase-associated receptor response?
- cytokines is the main ligand that binds to the tyrosine kinase-associated receptor to 2 receptor monomers simultaneously
- this brings them together
- 1 kinase phosphorylates the other in an area called the the activation lip- JAK
- JAK moves out of the active site and binds to ATP leading to more kinase activity
- enhanced kinase phosphorylates more tyrosine residues on the intracellular portion of the receptor
- phosophtyrosines serve as docking sites for SH2 domain containing proteins like STAT
