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)


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).


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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Darnell, J.E., Jr., 1997, STATs and gene regulation.Science277:1630–1635.PubMedCrossRefGoogle Scholar
  2. 2.
    Ndubuisi, M.l., Guo, G.G., Fried, V.A., Ettinger, J.D. and Sehgal, P.B., 1999, Cellular physiology of STAT3: where’s the cytoplasmic monomer?J. Biol. Chem.274: 25499–25509.PubMedCrossRefGoogle Scholar
  3. 3.
    Sehgal, P.B., 2000, STAT-signalling through the cytoplasmic compartment: consideration of a new paradigm.Cell. Signalling12: 525–535.PubMedCrossRefGoogle Scholar
  4. 4.
    Qureshi, S.A., Salditt-Georgieff, M., and Darnell, J.E., Jr., 1995, Tyrosine­phosphorylated Statl and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3.Proc. Natl. Acad. Sci. USA92: 3829–3833.PubMedCrossRefGoogle Scholar
  5. 5.
    Becker, S., Corthals, G.L., Aebersold, R., Groner, B., and Muller, C.W., 1998, Expression of a tyrosine phosphorylated, DNA binding STAT3ß dimer in bacteria.FEBS Lett.441: 141–147.PubMedCrossRefGoogle Scholar
  6. 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
  7. 7.
    Collum, R.G., Brutsaert, S., Lee, G., and Schindler, C., 2000, A Stat3-interacting protein (StIP1) regulates cytokine signal transduction.Proc. Natl. Acad. Sci. USA97: 10120–10125.PubMedCrossRefGoogle Scholar
  8. 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
  9. 9.
    Rayanade, R.J., Ndubuisi, M.I., Etlinger, J.D., and Sehgal, P.B., 1998, Regulation of IL-6 signaling by p53: STAT3- and STATS-masking in p53-Val-135-containing human hepatoma Hep3B cell lines.J. Immunol.161:325–334.PubMedGoogle Scholar
  10. 10.
    Yeung, Y.G., Wang, Y., Einstein, D.B., Lee, P.S.W., and Stanley, E.R., 1998, Colony-stimulating factor-1 stimulates the formation of multimeric cytosolic complexes of signaling proteins and cytoskeletal components in macrophages.J. Biol. Chem.273:17128–17137.PubMedCrossRefGoogle Scholar
  11. 11.
    Rayanade, R.J., Patel, K., Ndubuisi, M.I., Sharma, S., Omura, S., Etlinger, J.D., Pine, R., and Sehgal, P.B., 1997, Proteasome-and p53-dependent masking of signal transducer and activator of transcription (STAT) factors.J. Biol. Chem.272:4659–4662.PubMedCrossRefGoogle Scholar

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

Personalised recommendations