JAK-STAT Signalling Pathway

Summary

The JAK-STAT signaling pathway is crucial for transmitting signals into the nucleus to initiate gene expression, often utilizing cytokine-mediated signals. This video breaks down the pathway where cytokine signals, such as interferon and interleukin, are received by receptors and activate JAK proteins, leading to a series of phosphorylation events. This cascading effect creates docking sites for STAT proteins, which upon phosphorylation, dissociate from the receptor, dimerize, and translocate to the nucleus. In the nucleus, they bind to DNA to initiate transcription and gene expression, demonstrating the intricacies of cellular communication.

Highlights

• The JAK-STAT pathway relays information from cell membrane to nucleus ⚡
• Cytokine signals like interferon and interleukin trigger this pathway 📞
• JAK proteins phosphorylate each other to enhance activity 🔄
• Phosphorylated JAKs create docking sites for STAT proteins 🚌
• STAT proteins, after docking and phosphorylation, form dimers 🚸
• STAT dimers navigate to the nucleus to instigate gene transcription 🗝️
• This pathway exemplifies efficient cellular signaling and gene expression 🌐

Key Takeaways

• JAK-STAT pathway is pivotal for gene expression via signal transduction 🚀
• Cytokine signals include interferon, interleukin, and growth factors 📶
• JAK proteins activate through mutual phosphorylation ⚡
• Phosphorylated JAKs create docking sites for STAT proteins 🛬
• STAT proteins, once phosphorylated, dimerize and enter the nucleus 🧬
• In the nucleus, STAT dimers bind to DNA and trigger transcription 📝
• Understanding JAK-STAT is crucial for insights into cellular communication 🔍

Overview

The JAK-STAT signaling pathway serves as a critical communication channel within cells, translating outside signals into gene expression responses inside the nucleus. This video delves deep into how cytokines like interferon and interleukin activate receptors that subsequently engage JAK proteins, kickstarting a cascade of phosphorylation activities that are central to this pathway.

As the intricate pathway unfolds, JAK proteins undergo a mutual phosphorylation process, heightening their kinase activity to prepare the cellular stage for STAT proteins. These STAT proteins, upon binding to phosphorylated JAK sites, undergo their own activation via phosphorylation, setting the scene for their crucial role in nuclear translocation.

Once activated, STAT proteins dimerize—a process necessary for their journey to the nucleus. It's within this cellular core that they bind to DNA with precision, facilitating the transcription necessary for gene expression. Understanding this pathway not only highlights the elegance of cellular communication but also underscores its importance in biological processes and disease mechanisms.

Chapters

• 00:00 - 00:30: Introduction to JAK-STAT Signaling Pathway The chapter titled 'Introduction to JAK-STAT Signaling Pathway' focuses on the JAK-STAT signaling pathway, emphasizing its role as a critical route for transmitting information into the nucleus for gene expression. The pathway is described as being activated by a cytokine-mediated signal, which can take the form of interferons. The discussion builds upon previous knowledge about the components involved in the JAK-STAT pathway.
• 00:30 - 01:00: Cytokine Signal and Receptor Interaction In this chapter, the focus is on cytokine signals and their interaction with receptors. It explains how interleukin and various growth factors relate to the plasma membrane, which contains Jak-STAT components. These components are partly located outside the cell and partly within the intracellular region. The chapter details the structure and function of cytokine receptors, indicating that they are mostly dimers and interact with ligands, playing a crucial role in signal transduction.
• 01:00 - 01:30: JAK Proteins Association and Activation The chapter discusses the association and activation of JAK (Janus kinase) proteins in the intracellular part of cytokine receptors. JAK proteins, specifically JAK1 and JAK2, are associated with cytokine receptors. When a signal in the form of a cytokine is present, it is received by the receptors. The binding of cytokines to their receptors leads to an arrangement or activation process involving these JAK proteins.
• 01:30 - 02:00: Phosphorylation of Tyrosines and STAT Protein Docking The chapter titled 'Phosphorylation of Tyrosines and STAT Protein Docking' begins with the description of how JAK kinases are brought into close proximity, leading to their mutual phosphorylation. This mutual phosphorylation activates their tyrosine kinase domains, allowing the JAK kinases to phosphorylate tyrosines on cytokine receptors. This phosphorylation creates phosphotyrosine docking sites for STAT proteins, which is illustrated in the accompanying diagram.
• 02:00 - 02:30: STAT Protein Phosphorylation and Dimerization The chapter focuses on the phosphorylation and dimerization processes of STAT proteins. It explains how Dok2 phosphotyrosine sites are linked to the SH2 domain of STAT proteins. This facilitates the interaction of STAT proteins with phosphorylated tyrosine residues. STAT proteins comprise various domains, which are briefly mentioned, with a prompt to refer to a previous video for more details. Upon STAT proteins binding to specific phosphotyrosine sites on receptors, which get phosphorylated by JAG, a sequence of cellular events depicted in the diagram ensues.
• 02:30 - 03:00: Translocation and Gene Expression The chapter "Translocation and Gene Expression" delves into the dissociation of proteins from receptors due to phosphorylation. This process involves the detachment of a sted protein from the phosphotyrosine. After dissociation, the SS-domain on the LEAs binds to the phosphotyrosine on another stat molecule. This action results in the formation of either a homodimer, if stat proteins are the same, or a heterodimer if they are different. The chapter concludes with the finalized state of the stat protein formation process.
• 03:00 - 03:30: Conclusion The chapter titled 'Conclusion' discusses the JAK-STAT signaling pathway. It explains how a dimer forms and translocates to the nucleus, facilitated by the DNA binding domain of the STAT protein that attaches to the DNA. This attachment initiates transcription, leading to gene expression. The pathway is characterized as being mediated by cytokine signals. The speaker concludes by suggesting viewers watch a previous video for insights into the detailed structure of Janus kinase and STAT protein.

JAK-STAT Signalling Pathway Transcription

• 00:00 - 00:30 in the previous video we discussed about the components of jak-stat pathway and now in this video we'll be discussing about the jak-stat signaling pathway this pathway is one of the dag routes to transmit information into nucleus for gene expression in this pathway the cytokine mediated signal activates the components of this pathway the cytokine signal can be in the form of interferon
• 00:30 - 01:00 interleukin and some growth factors the plasma membrane has got these jak stat components in it while we see some part of it lies outside the cell whereas some part is in the intracellular region the part of complex which is in the extracellular region comprises of receptors cytokine receptors and these cytokine receptors are mostly Deimos and shows interaction in the form of ligand
• 01:00 - 01:30 binding off psycho kinds whereas in the intracellular part the cytokine receptors are associated with two Jack proteins Jen's Kenny's as shown in figure these are the 2j proteins associated with cytokine receptors when there is presence of any signal in the form of cytokine like this as shown in the figure it's received by receptors after cytokine binds towards their receptors it's finding all those the arrangement
• 01:30 - 02:00 and brings through jags into close proximity with these two Jack turns phosphorylate each other one Jack postulates the other thereby increasing the activity of their tyrosine kinase domains in the next step we see these phosphorylated Jack kinases then phosphorylate tyrosines on the cytokine receptors creating phosphotyrosine docking sites for sted proteins as shown in the diagram in the proceeding step the stat proteins
• 02:00 - 02:30 dok2 phosphotyrosine sites like this and it's by the sh2 domain ofsted protein which mediates the talking of sted tools phosphorylated tyrosine because this stat has different types of domains if you won't see what stat is you can see the previous video after stats talk on specific phosphotyrosine on the receptor that jag phosphorylates them as shown in the diagram and then population of stead
• 02:30 - 03:00 proteins causes the stats to dissociate from receptor so the phosphorylation detach a sted protein from the phosphotyrosine after the dissociation the SS - domain on the LEAs it's dead now mediates its binding - phosphotyrosine on another stat molecule forming idris tied homodimer if stat proteins are saying or heterodimer if stat proteins are different so finally we have stat
• 03:00 - 03:30 diamond now and this dimer translocates to the nucleus while by the help of DNA binding domain of stat protein attaches itself to the DNA and initiates the transcription and finally we have the gene expression so this is how the jak stat pathway works in with the help of cytokine mediated signals if you won't see the detailed structure of Janus kinase and state protein you can watch my previous video thanks for
• 03:30 - 04:00 watching this video if you liked it give it a thumbs up and make sure subscribe this channel Thanks