4.1 Flashcards
Tyrosine Kinases (40 cards)
What distinguishes kinase-linked receptors from other receptor types like GPCRs?
They have intrinsic or linked kinase domains, allowing phosphorylation-based signalling.
What is the main function of phosphorylation in signal transduction?
Acts as an on/off regulatory switch controlling protein activity.
What enzymes are responsible for adding and removing phosphate groups?
Kinases add (phosphorylate); phosphatases remove (dephosphorylate).
What is the most common post-translational modification?
Phosphorylation.
What percentage of cellular proteins are phosphorylated?
About 30%.
What residues are commonly phosphorylated by protein kinases?
Serine (S), threonine (T), and tyrosine (Y).
What are the two main groups of kinases based on substrate preference?
Serine/threonine kinases (S/T) and tyrosine kinases (Y).
What domains compose a kinase’s catalytic region?
N-terminal β-sheet lobe and C-terminal α-helix lobe.
Where do ATP and substrate bind?
In the catalytic cleft between the two lobes.
How is specificity for S, T, or Y achieved?
By the surrounding amino acid context and cleft depth (Y = deeper).
What is the significance of tyrosine phosphorylation in cancer?
It’s less common than S/T phosphorylation but is strongly linked to cancer due to unregulated signalling.
What proportion of oncogenes are tyrosine kinases?
About 30%.
What are proto-oncogenes?
Normal genes that can become oncogenes if mutated or overexpressed.
What domains are typically found in RTKs?
Extracellular ligand-binding, single transmembrane, intracellular tyrosine kinase, juxtamembrane, and C-terminal regions.
How many RTK families and receptors are there?
20 families; 58 receptors.
How many RTKs are implicated in cancer?
At least 31 are mutated or overexpressed in cancers.
What triggers RTK activation?
Ligand binding → receptor dimerisation → trans-autophosphorylation.
What happens after the kinase domains come together?
They phosphorylate each other’s activation loops and regulatory tyrosine residues.
What do phosphorylated tyrosines on RTKs serve as?
Docking sites for SH2/PTB-domain-containing proteins.
What ligand activates CSF-1R?
CSF-1 (homodimer).
What is the key phosphorylation site for CSF-1R activation?
Tyrosine 807 (Y807).
How many tyrosine residues are phosphorylated on CSF-1R?
Seven.
What terminates RTK signalling?
Phosphatases (dephosphorylation) and ubiquitylation (degradation).
How are non-RTKs activated?
By dimerisation of associated receptors that lack intrinsic kinase domains.
