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Cytokine-induced STAT signalling through the cytoplasmic compartment

  • Pravin B. Sehgal
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 495)

Abstract

The standard model for cytokine-induced signalling through the cytoplasmic compartment by the family of proteins designated “STATs” (“signal transducers and activators of transcription”) posits that STAT proteins exist in the cytoplasmic compartment as monomers which are activated by tyrosine (Tyr) phosphorylation by receptor-associated Janus family kinases (JAKs), the Tyr-phosphorylated STATs dimerize and then the STAT dimers translocate to the nucleus’. In previous work from this laboratory we have evaluated whether STAT proteins existed in the cytoplasmic compartment as free monomers and whether these then dimerized upon Tyr-phosphorylation following cytokine induction23. We used gel-filtration chromatography through Superose-6 columns for sizing STAT protein complexes, and observed that STAT1, STAT3, STAT5a, and STAT5b existed in complexes of size 200-400 kDa and 1-2 MDa in the cytosolic compartment of hepatocytes (rat liver or human Hep3B hepatoma cell lines)23. Upon stimulation with interleukin-6 (IL-6) there was no appreciable shift in size of the Tyr-phosphorylated STAT3 that would indicate the occurrence of a simple monomer to dimer transition23. These observations, among others, led us to propose that STAT proteins existed in the cytoslic compartment not as free monomers but as high molecular weight complexes of size 200-400 kDa (“statosome I”) and 1-2 Mda (“statosome II”) in association with othor proteins which regulated STAT function and trafficking through the cytoplasmic compartment 2,3(Fig.1).

Keywords

Hep3B Cell Cytoplasmic Compartment Free Monomer Nucleus Translocation Cytosolic Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Pravin B. Sehgal
    • 1
  1. 1.Departments of Cell Biology & Anatomy,and MedicineNew York Medical College,ValhallaNew YorkUSA

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