Cell Signalling 2 Flashcards
Define;
- phosphate
- kinase
- protein kinases
Phosphate - composed of 1 Phosphorous atom and 4 Oxygen atoms
kinase - enzyme that transfers the terminal phosphate group from ATP to a substrate
Protein kinases transfer the
phosphate group to specific serine, threonine or tyrosine residues in proteins.
Describe the enzyme-coupled receptor structure
Ligand binding domain - extracellular region that allows for easy access and activation to the receptor
Transmembrane domain - a series of hydrophobic amino acids that tethers the receptor to the cell membrane
Intracellular domain - either contains intrinsic catalytic activity or tightly bound to an enzyme
Describe the main stages of Receptor Tyrosine Kinase activation
When the ligand binds, the receptors form dimers
Receptor’s enzymatic activity
of the intracellular region - tyrosine kinase domain is turned on
The receptor units cross-
phosphorylate
Phosphate groups on the receptor form the basis for docking sites so other proteins can bind and undergo phosphorylation on tyrosines for activation
Docked proteins relay the signal
Differentiate between Protein Kinases and Guanine Nucleotide Exchange Factors
Protein kinases;
- Phosphorylate proteins to regulate function
- target serine, threonine, or tyrosine residues
- mechanism of action is transfer of phosphate to ADP
- Signal amplification through phosphorylation
Guanine Nucleotide Exchange Factors;
- facilitate GDP-GTP exchange on G proteins
- target GTP-binding proteins
- mechanism of action is to promote GTP binding to G proteins
- activate G proteins as molecular switches
What are activated intracellular proteins bound by ?
Intracellular signalling proteins docked on activated RTKs usually bind phosphorylated tyrosines through Src Homology 2 (SH2) domains.
Discuss signalling pathways activated by Receptor Tyrosine Kinases
RTKs: Dimerize and autophosphorylate upon ligand binding.
Main Pathways:
RAS-MAPK: Regulates proliferation/differentiation via RAF → MEK → ERK.
PI3K-Akt: Promotes survival and growth via PIP3 → Akt activation.
PLCγ: Triggers Ca²⁺ release (IP3) and PKC activation (DAG).
JAK-STAT: Directly regulates gene expression through STAT activation.
Functions: Control proliferation, survival, growth, and differentiation.
What is small GTPase RAS ?
First commonly activated molecule after RTK activation is a protein called Ras
Molecular switch that alternates between GTP bound (on) and GDP bound (off)
GTP-bound Ras associates with the plasma membrane,
diffuses laterally, and activates other proteins at the cell surface
Describe the RAS-MAPK pathway:
Ras activates a chain reaction of phosphorylation events involving mitogen-activated protein kinases (MAPKs)
MAPKs usually held together by scaffolds - they ensure that specific MAPKs are activated
Describe Activation of RAS-MAPK by EGF:
EGF Binding: EGF binds to EGFR extracellular domain.
Dimerization: EGFR dimerizes and autophosphorylates on tyrosine residues.
Adaptor Proteins: Phosphorylated EGFR recruits Grb2 (adaptor protein) and Sos (guanine nucleotide exchange factor).
RAS Activation: Sos activates RAS by exchanging GDP for GTP.
MAPK Cascade: Active RAS-GTP activates RAF → RAF activates MEK → MEK activates ERK (MAPK).
Nuclear Response: ERK translocates to the nucleus and phosphorylates transcription factors, regulating gene expression.