positive regulation of receptor signaling pathway via JAK-STAT

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the JAK-STAT signaling pathway activity. [GOC:bf]

Positive regulation of receptor signaling pathway via JAK-STAT is a complex biological process that involves the activation of intracellular signaling pathways by extracellular ligands. This pathway is crucial for a wide range of cellular functions, including cell growth, differentiation, and survival. Here's a detailed description of the process:

1. **Ligand Binding and Receptor Dimerization:** The process begins with the binding of a specific ligand to its cognate receptor on the cell surface. This binding event induces a conformational change in the receptor, promoting its dimerization. The receptor can be a cytokine receptor, such as the erythropoietin receptor (EPO-R), or a growth factor receptor, such as the growth hormone receptor (GHR).

2. **JAK Kinase Activation:** Upon dimerization, the receptor molecules come into close proximity, bringing together associated Janus kinase (JAK) molecules. The JAKs are tyrosine kinases that become activated upon receptor dimerization. Activation of JAKs involves trans-phosphorylation, where one JAK molecule phosphorylates another JAK molecule within the dimer.

3. **STAT Recruitment and Phosphorylation:** Once activated, JAKs phosphorylate tyrosine residues on the cytoplasmic tails of the receptor. These phosphorylated tyrosines serve as docking sites for signal transducer and activator of transcription (STAT) proteins. STAT proteins are transcription factors that are activated by phosphorylation. The STAT proteins bind to the phosphorylated tyrosines on the receptor, where they themselves are phosphorylated by JAKs.

4. **STAT Dimerization and Nuclear Translocation:** After phosphorylation, STAT proteins dimerize through their SH2 domains, which recognize phosphotyrosines. The dimerized STAT proteins then translocate to the nucleus through the nuclear pores.

5. **Gene Transcription Activation:** In the nucleus, the dimerized STAT proteins bind to specific DNA sequences called STAT response elements (SREs) located in the promoter regions of target genes. This binding activates transcription of these genes, leading to the synthesis of proteins that mediate the biological effects of the signal.

6. **Negative Regulation:** The JAK-STAT pathway is subject to negative regulation to prevent excessive signaling. This regulation involves several mechanisms, including:
* **Protein tyrosine phosphatases (PTPs):** PTPs dephosphorylate JAKs and STAT proteins, reducing their activity.
* **Suppressors of cytokine signaling (SOCS) proteins:** SOCS proteins inhibit JAK activity and promote the degradation of receptor and STAT proteins.
* **Feedback inhibition:** STAT proteins can directly inhibit their own activation by interfering with JAK activity.

7. **Biological Effects:** Activation of the JAK-STAT pathway leads to a wide range of biological effects, including:
* **Cell proliferation and survival:** The pathway is involved in the growth and survival of various cell types, such as hematopoietic cells, immune cells, and epithelial cells.
* **Differentiation:** The pathway is involved in the development of specific cell types, such as red blood cells, immune cells, and neurons.
* **Immune regulation:** The pathway is crucial for the regulation of the immune response, including the production of cytokines and the activation of immune cells.

In summary, positive regulation of receptor signaling pathway via JAK-STAT is a complex process involving multiple steps, from ligand binding to gene transcription activation. This pathway is critical for a variety of cellular processes and plays a crucial role in maintaining cellular homeostasis. Its dysregulation is associated with several disease conditions, including cancer, autoimmune diseases, and inflammatory disorders.'
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Proteins (19)

Compounds (573)