Peptide Hormones
Definition: Small protein molecules that act as signalling molecules in the body.
Mechanism: Bind to cell surface receptors as they cannot cross the plasma membrane.
Receptors: Typically G-protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs).
G-Protein-Coupled Receptors (GPCRs)
Upon binding of the hormone, the GPCR undergoes a conformational change.
This activates the associated G-protein by exchanging GDP for GTP. The activated G-protein then dissociates into α and βγ subunits, which interact with other intracellular proteins to propagate the signal.
Receptor Tyrosine Kinases (RTKs)
- Hormone binding induces dimerization of the RTKs.
- Dimerization activates the intrinsic kinase activity, leading to autophosphorylation on tyrosine residues.
- These phosphorylated tyrosines serve as docking sites for downstream signalling proteins.
Growth Factors
- Definition: Proteins that stimulate cell proliferation, differentiation, and survival.
- Examples: Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF).
- Receptors: Mostly receptor tyrosine kinases (RTKs).
- Mechanism: Binding to RTKs causes dimerization and autophosphorylation, triggering downstream signalling cascades.
Mechanism
- MAPK/ERK Pathway: Activated RTKs often recruit and activate the Ras protein, which then triggers a kinase cascade involving RAF, MEK, and ERK.
- PI3K/AKT Pathway: RTKs can also activate phosphoinositide 3-kinase (PI3K), which converts PIP2 to PIP3, leading to the activation of AKT. AKT promotes cell survival and growth.