Bio 3105 - Cytokines & Tyrosine Kinase Associated Receptors
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What are Cytokine Receptors associated with?
How is the Jak-STAT Pathway Activated?
Cytokines and Cytokine Receptors
What Does JAK stand for?
How is Transcription activated by Jak-STAT?
Erythropoietin Binding -> Epo Receptor -> Tyrosine Kinases Activate ->Transautophosphorylation -> JAK Binds -> STAT Binds (SH2) -> Jak Phosphorylates STAT -> STAT Moves to Nucleus
What is STAT?
A Transcription Factor phosphorylated by JAK.
How do Interferons Lead to Cross-Phosphorylation?
Binding of Extracellular Interferon -> Dimerization -> Phosphorylation of Adjecent Jaks -> Phosphorylation of Tyrosine
What Happens to STATs after activation?
STATS dissociate from Receptor -> STATs dimerize (SH2 Domains) -> Dimers Migrate to Nucleus -> Binding to Interferon Response Elements (Genes)
How Are Mature Red Blood Cells formed?
Hamatopoieitic Stem Cell -> Erythroid Progenitor -> Erythropoieitin -> Cell Division & Further Maturation -> Red Blood Cells
What happens to Erythroid Progenitor Cells without Erythropoieitin?
They die by Apoptosis.
What is an example of a Cytokine interacting with other Signalling Pathways?
RTK's and Cytokine Receptors Activating Phospholipase C and PI-3 Kinase
What do TGFβ Receptors do?
- TGFβ's have a number of functions
- Prevents Cell Division
- Promotes Expression of Cell Adhesion
- Promotes Expression of Extracellular Matrix Molecules
What are TGFβ Receptors?
What does an Activated TGFβ do?
Directly Phosphorylates Transcription Factors
How if TGFβ formed?
- A Precursor is Secreted
- Proteolytic Cleavage
- Dimerization & Binding by LTBP
- Proteolysis of LTBP releases mature TGFβ
What is the ligand for β-Glycan Receptors?
How is Smad 2 (or 3) recruited from extracellular TGFβ?
TGFβ -> Type II TGFβ Receptor -> Binding With Type I TGFβ Receptor -> Type II-Type I Receptor Complex -> Transautophosporylation -> Phosphorylation and/or recruiting of Smad 2/3
What is the structure of TGFβ?
Three Polypeptides; RI, RII, RIII
What is the role of the polypeptide RII in TGFβ?
Autophosphosphorylating itself and RI on TGFβ binding.
What is the effect of binding TGFβ to RII?
Stimulating binding of RI and phosphorylation of RI.
What happens to Smads after dissociation from TGFβ receptors?
- Smad 2/3 oligomerizes with Smad 4.
- The Oligomer then migrates to the nucleus.
- Binding of the Oligomer to the TGF-β Response Element.
- Binding of Regulatory Proteins
What is another term that could be used for the Smad 2/3-Smad 4 Oligomer?
A Transcriptional Factor
How does the Smad Transcription Factor enter the nucleus?
- It's Nuclear Localization Signal
What is NLS shorthand for?
Nuclear Localization Signal
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