Enzyme-Coupled Receptors Overview
Basic Properties
- Bind signaling molecules extracellularly.
- Regulate cell growth, proliferation, differentiation, and survival.
- Can directly reconfigure the cytoskeleton.
- Largest class are receptor tyrosine kinases (RTKs).
RTK Activation Steps
- Ligand binding causes dimerization of RTKs.
- Dimerized RTKs undergo trans-autophosphorylation.
- Intracellular signaling proteins are recruited and activated.
- Turned off by protein tyrosine phosphatases or receptor internalization.
Intracellular Signaling Molecules Activated by RTKs
- Ras (monomeric GTPase)
- Phosphoinositide 3-kinase (PI 3-kinase)
- Phospholipase C (produces DAG and IP3)
Ras Signaling Mechanism
- Indirectly activated by RTKs.
- Initiates the MAP kinase signaling pathway leading to cell proliferation.
- Mutated Ras proteins are linked to cancer, causing continuous activation of cell cycles.
PI 3-Kinase Function
- Activated by RTKs; converts inositol phospholipids to phosphorylated forms.
- Recruitment of signaling proteins (e.g., Akt) for cell survival and growth.
- Akt phosphorylates targets to inhibit cell death, promoting survival.
Interconnection of Signaling Pathways
- RTKs and G-protein-coupled receptors (GPCRs) activate complex signaling networks.
- Multiple intracellular signaling pathways are interconnected.
Delta-Notch Signaling
- Notch is a transcription regulator controlling gene expression directly.
- Plays a key role in the development of neural cells.
Differences in Plant Cell Signaling
- Plants use different strategies involving receptor serine/threonine kinases.
- Ethylene receptors can inhibit repression leading to gene activation.
- Intracellular signaling proteins integrate multiple signals for a net outcome based on signal strength and quantity.
Exam Preparation Tips
- Understand key signaling pathways and their effects on cellular processes.
- Identify roles of specific proteins (Ras, Akt, PI 3-kinase) in signaling.
- Be aware of differences between animal and plant signaling methods.