Intercellular Signaling part 4

Summary

This video explores surface receptors connected to enzymes, specifically focusing on receptor tyrosine kinases (RTKs). It discusses various RTKs, such as those activated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). The video also highlights how these receptors initiate processes like angiogenesis and cellular responses via phosphorylation. Additionally, it covers how proteins such as PI-3 kinase and PDK1 interact within these signaling pathways, affecting cell survival and inhibiting apoptosis. The importance of these mechanisms in regulating cell growth, survival, and response to injury is emphasized.

Takeaways

• 😀 Receptors can be connected to enzymes, such as tyrosine kinase receptors, serine-threonine kinase receptors, and guanylate cyclase receptors.
• 😀 Tyrosine kinase receptors activate enzymes that catalyze GTP to cyclic GMP, a process important in cell signaling.
• 😀 Tyrosine kinase receptors have different types, such as Epidermal Growth Factor (EGF) receptors, Platelet-Derived Growth Factor (PDGF) receptors, and Vascular Endothelial Growth Factor (VEGF) receptors.
• 😀 When VEGF receptors are activated, they stimulate angiogenesis, the formation of new blood vessels, often in response to injury.
• 😀 Tyrosine kinase receptors are located in the plasma membrane with extracellular domains that bind signaling molecules and intracellular kinase domains that activate downstream signals.
• 😀 Upon ligand binding, the extracellular domain of the receptor changes shape, leading to the activation of the intracellular kinase domain, which phosphorylates tyrosine residues.
• 😀 Phosphorylation of tyrosine residues enables the receptor to interact with intracellular signaling proteins, leading to diverse cellular responses.
• 😀 The variety of cellular responses is determined by the specific proteins recruited to the phosphorylated sites on the receptor, such as PI-3 kinase, phospholipase C, or other signaling molecules.
• 😀 PI-3 kinase activation leads to phosphorylation of phosphoinositides, which generates docking sites for proteins with pleckstrin homology (PH) domains.
• 😀 Activation of tyrosine kinase receptors by ligands like PDGF or survival signals ensures cell survival by activating pathways that inhibit apoptosis and support cell growth.

Q & A

What is the role of surface receptors mentioned in the video?

Surface receptors, like the ones connected to proteins such as tyrosine kinase receptors, play a critical role in cellular signaling by detecting and responding to external signals, which then trigger intracellular pathways.

What are some examples of receptors connected to enzymes as mentioned in the video?

Some examples include tyrosine kinase receptors, serine/threonine kinase receptors, and guanylate cyclase receptors. These receptors activate enzymes that can regulate various cellular functions.

What happens when the VEGF receptor is activated?

When the VEGF (vascular endothelial growth factor) receptor is activated, it stimulates angiogenesis, the formation of new blood vessels, usually in areas of the body that have been injured or are lacking proper blood supply.

How does receptor activation lead to a structural change in the receptor itself?

Upon ligand binding to the extracellular domain of the receptor, a conformational change occurs in the receptor, leading to activation of the intracellular kinase domain, which in turn activates signal transduction pathways inside the cell.

What is the significance of receptor dimerization?

Dimerization refers to the process where two receptor monomers come together upon ligand binding. This dimerization is crucial for activating the receptor's intracellular signaling pathways, often involving phosphorylation of specific tyrosine residues.

What is the role of tyrosine phosphorylation in receptor signaling?

Tyrosine phosphorylation is a key event in receptor signaling, where specific tyrosine residues on the receptor are phosphorylated. This phosphorylation creates docking sites for intracellular signaling proteins, triggering various cellular responses.

What are some examples of intracellular signaling proteins that interact with phosphorylated receptors?

Examples include proteins with Src homology (SH2) domains, such as PI3 kinase, which is activated by binding to phosphorylated tyrosine residues. These proteins help propagate the signal inside the cell.

How does PI3 kinase contribute to cellular signaling?

When activated, PI3 kinase phosphorylates a lipid in the cell membrane called phosphatidylinositol, generating phosphoinositide derivatives, which serve as docking sites for other signaling proteins involved in processes like cell growth and survival.

What happens when the receptor tyrosine kinase is activated by survival signals?

When activated by survival signals, receptor tyrosine kinases promote cell survival by preventing apoptosis. They activate proteins that inhibit apoptosis pathways, ensuring the cell remains alive.

What is the role of PDK1 in the activation of survival pathways?

PDK1 (3-phosphoinositide-dependent kinase-1) is crucial in activating survival pathways. It activates other proteins, such as Akt, which prevent apoptosis and promote cell survival by influencing various cellular processes.