Cytokine-induced STAT signalling through the cytoplasmic compartment
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 induction2’3. 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)2’3. 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 transition2’3. 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).
KeywordsHep3B Cell Cytoplasmic Compartment Free Monomer Nucleus Translocation Cytosolic Complex
Unable to display preview. Download preview PDF.
- 6.Lackmann, M., Harpur, A.G., Oates, A.C., Mann, R.J., Gabriel, A., Meutermans, W., Alewood, P.F., Kerr, I.M., Stark, G.R., and Wilks, A.F., 1998, Biomolecular interaction analysis of IFNy-induced signaling events in whole-cell lysates: prevalence of latent STAT1 in high-molecular weight complexes.Growth Factors16:39–51.PubMedCrossRefGoogle Scholar
- 8.Haspel, R.L., Salditt-Georgieff, M., and Darnell, J.E., Jr., 1996, The rapid inactivation of nuclear tyrosine phosphorylated STAT1 depends upon a protein tyrosine phosphatase.EMBO J22:6262–6268.Google Scholar