Intercellular Signaling part 5

Summary

This video script explores various intracellular signaling pathways activated by receptor tyrosine kinases, GPCRs, and cytokines. It discusses the roles of proteins like Ras, Rap, and Stat in cellular processes such as growth, adhesion, and gene expression. Key mechanisms such as MAP kinase activation, JAK-STAT signaling, and TGF-beta receptor pathways are explained in detail. The script also covers notch signaling, involving a process of proteolysis that regulates differentiation in cells. Through this, it provides insights into complex cellular communication, essential for maintaining cellular functions and regulating immune responses.

Takeaways

• 😀 Ras proteins are monomeric GTPases that relay signals from activated receptor tyrosine kinases (RTKs), involved in cell growth and adhesion.
• 😀 Ras activates the MAP kinase pathway, which helps regulate various proteins, including structural proteins and gene regulators, by phosphorylation.
• 😀 Phosphorylation of regulatory proteins can alter their function and gene expression, leading to cellular changes.
• 😀 There is overlap in signaling pathways activated by GPCRs (G-protein-coupled receptors) and RTKs, especially in activating PLC (phospholipase C).
• 😀 PLC, when activated, triggers CAM kinase and PKC, which impact protein regulation and cellular structure.
• 😀 Cytokine receptors, like interferons, are involved in immune responses, activating the JAK-STAT pathway to regulate gene expression.
• 😀 Interferons are classified into type 1 (alpha and beta) and type 2, produced by virus-infected cells and immune cells like T-cells and macrophages.
• 😀 Cytokine receptors bind to ligands like interferons, activating JAK kinases, which phosphorylate proteins for further signaling.
• 😀 TGF-beta (Transforming Growth Factor-beta) activates serine-threonine kinase receptors, influencing gene regulation through the SMAD signaling pathway.
• 😀 Notch signaling is a contact-dependent mechanism that involves Delta-Notch interaction, crucial for nervous system development by regulating cell differentiation.

Q & A

What are Ras proteins, and what role do they play in cellular signaling?

Ras proteins are monomeric GTPases involved in transmitting signals from activated receptor tyrosine kinases (RTKs). They play a critical role in regulating cell growth, differentiation, and adhesion by triggering the MAP kinase signaling cascade.

What is the MAP kinase pathway, and how is it activated?

The MAP kinase pathway is a signaling cascade that regulates gene expression and cell functions such as growth and differentiation. It is activated when Ras proteins bind to and activate various kinases, including MAPKKK, MAPKK, and MAPK, leading to the phosphorylation of target proteins.

How do GPCR and RTK signaling pathways overlap?

GPCR and RTK pathways overlap because both can activate shared signaling molecules like phospholipase C. This leads to the activation of kinases such as PKC and CAMK, which can affect protein structure and gene expression in cells.

What is the JAK-STAT pathway, and what role do cytokines play in it?

The JAK-STAT pathway is a signaling mechanism activated by cytokines. When a cytokine binds to its receptor, JAK kinases are activated, which in turn phosphorylate STAT proteins. These activated STAT proteins dimerize, enter the nucleus, and regulate gene expression important for immune responses and cell function.

How does the TGF-β signaling pathway work?

The TGF-β pathway is activated when TGF-β binds to its receptor, a serine/threonine kinase. This binding causes phosphorylation of Smad proteins, which then form complexes and translocate to the nucleus, where they regulate gene transcription involved in processes like cell differentiation and immune regulation.

What is the role of Notch signaling in cell differentiation?

Notch signaling plays a key role in determining cell fate, particularly in neural development. It involves interaction between Notch receptors and Delta ligands, leading to proteolytic cleavage of Notch. The cleaved fragment enters the nucleus and regulates genes involved in differentiation.

What happens when Notch is activated by Delta ligands?

When Delta ligands bind to Notch receptors, a proteolytic cleavage occurs, releasing the Notch intracellular domain. This fragment then translocates to the nucleus, where it interacts with transcription factors to regulate gene expression, affecting cell differentiation.

What is the importance of proteolysis in signaling pathways like Notch?

Proteolysis is crucial in certain signaling pathways like Notch, as it helps activate signaling molecules. In Notch signaling, the proteolytic cleavage of the Notch receptor releases an active fragment that enters the nucleus to regulate gene expression.

How do activated Ras proteins affect cell growth?

Activated Ras proteins affect cell growth by activating the MAP kinase pathway. This cascade leads to the phosphorylation of proteins involved in cell cycle progression and growth, promoting cell division and survival.

Why is the overlap between GPCR and RTK signaling pathways significant?

The overlap between GPCR and RTK signaling pathways is significant because it allows for more complex and integrated cellular responses. Both pathways can activate similar downstream signaling molecules, leading to coordinated changes in cell behavior, such as migration, adhesion, and gene expression.