Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

A role for Janus kinases in crosstalk between ErbB3 and the interferon-alpha signaling complex in myeloma cells

Oncogene volume 23, pages 1197–1205 (2004)Cite this article

Abstract

Receptor crosstalk is an emerging and recurrent theme in cytokine and growth factor signaling; however, insight into the mechanism(s) underlying these interactions remains limited. Recently, we reported that crosstalk occurs between ErbB3 and the interferon alpha (IFN-α) signaling complex in the myeloma cell line KAS-6/1 and that this crosstalk contributes to the regulation of cell proliferation. In this study, we examined the mechanism underlying the transactivation of ErbB3 in the IFN-α growth-responsive KAS-6/1 cells. The examination of IFN-α receptor 1 and 2 (IFNAR1 and IFNAR2) levels revealed that the KAS-6/1 cell line overexpresses IFNAR1 relative to other myeloma cell lines that are growth arrested by IFN-α. Subsequent investigation of Tyk2, which is constitutively associated with IFNAR1, demonstrated that Tyk2 activation is uniquely sustained in the KAS-6/1 cell line following IFN-α stimulation. Interestingly, silencing of Tyk2 expression via siRNA resulted in attenuation of ErbB3 transactivation. However, inhibition of Jak1 expression also decreased IFN-α-induced tyrosine phosphorylation of ErbB3. Finally, siRNA downregulation of Tyk2 and Jak1 was found to decrease IFN-α-stimulated proliferation. These findings validate our previous report of ErbB3 involvement in IFN-α-induced proliferation and further suggest that both Janus kinase members, Tyk2 and Jak1, play a role in the transactivation of ErbB3 in this model system.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Arora T, Floyd-Smith G, Espy MJ and Jelinek DF . (1999). J. Immunol., 162, 3289–3297.

  • Blade J, Lopez-Guillermo A, Tassies D, Montserrat E and Rozman C . (1991). Br. J. Haematol., 79, 523–525.

  • Brenning G, Ahre A and Nilsson K . (1985). Scand. J. Haematol., 35, 543–549.

  • Boundy V and Kovarik J . (2002). Neoplasma, 49, 349–355.

  • Buhring HJ, Sures I, Jallal B, Weiss FU, Busch FW, Ludwig WD, Handgretinger R, Waller HD and Ullrich A . (1995). Blood, 86, 1916–1923.

  • Colamonici OR, Uyttendaele H, Domanski P, Yan H and Krolewski JJ . (1994a). J. Biol. Chem., 269, 3518–3522.

  • Colamonici OR, Yan H, Domanski P, Handa R, Smalley D, Mullerman J, Witte M, Krishnan K and Krolewski JJ . (1994b). J. Biol. Chem., 269, 3518–3522.

  • DiGiovanna MP, Chu P, Davison TL, Howe CL, Carter D, Claus EB and Stern DF . (2002). Cancer Res., 62, 6667–6673.

  • Dondi E, Pattyn E, Lutfalla G, Van Ostade X, Uze G, Pellegrini S and Tavernier J . (2001). J. Biol. Chem., 276, 47004–47012.

  • Dumont JE, Pecasse F and Maenhaut C . (2001). Cell. Signal., 13, 457–463.

  • Harari D and Yarden Y . (2000). Oncogene, 19, 6102–6114.

  • Hill SM . (1998). Anat. Rec., 253, 42–48.

  • Jelinek DF, Aagaard-Tillery KM, Arendt BK, Arora T, Tschumper RC and Westendorf JJ . (1997). J. Clin. Invest., 99, 447–456.

  • Jelinek DF, Walters DK, French JD, Arendt BA and Tschumper RC . (2003). Hematol. J., 4, S37.

  • Jourdan M, Zhang XG, Portier M, Boiron JM, Bataille R and Klein B . (1991). J. Immunol., 147, 4402–4407.

  • Krishnan K, Pine R and Krowlewski JJ . (1997). Eur. J. Biochem., 247, 298–305.

  • Kuhn DJ, Smith DM, Pross S, Whiteside TL and Dou QP . (2003). J. Cell. Biochem., 89, 824–836.

  • Long IS, Han K, Li M, Shirasawa S, Sasazuki T, Johnston M and Tsao MS . (2003). Mol. Cancer Res., 1, 393–401.

  • McManus TM, Haines BB, Dillon CP, Whitehurst CE, van Parijs L and Sharp PA . (2002). J. Immunol., 169, 5754–5760.

  • McManus TM and Sharp PA . (2002). Nat. Rev. Genet., 3, 737–747.

  • Novick D, Cohen B and Rubinstein M . (1994). Cell, 77, 391–400.

  • Olayioye MA, Beuvink I, Horsch K, Daly JM and Hynes NE . (1999). J. Biol. Chem., 274, 17209–17218.

  • Ragimbeau J, Dondi E, Alcover A, Eid P, Uze G and Pellegrini S . (2003). EMBO J., 22, 537–547.

  • Sawamura M, Murayama K, Ui G, Matsushima T, Tamura J, Murakami H, Naruse T and Tsuchiya J . (1992). Br. J. Haematol., 82, 631.

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL . (1987). Science, 235, 177–182.

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J and Norton L . (2001). N. Engl. J. Med., 344, 783–792.

  • Uddin S, Sher DA, Alsayed Y, Pons S, Colamonici OR, Fish EN, White MF and Platanias LC . (1997). Biochem. Biophy. Res. Commun., 235, 83–88.

  • Walters DK, French JD, Arendt BA and Jelinek DF . (2003). Oncogene, 22, 3598–3607.

  • Walters DK and Jelinek DF . (2002). Antisense Nucleic Acid Drug Dev., 12, 411–418.

  • Westendorf JJ, Ahmann GJ, Greipp PR, Witzig TE, Lust JA and Jelinek DF . (1996). Leukemia, 10, 866–876.

  • Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y and Kadowaki T . (1997). Nature, 390, 91–96.

Download references

Acknowledgements

We thank Renee Tschumper and Michael Bell for their technical expertise regarding data analysis.

Author information

Authors and Affiliations

  1. Department of Immunology, Tumor Biology Program, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, 55905, MN, USA

    Denise K Walters & Diane F Jelinek

Authors
  1. Denise K Walters
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane F Jelinek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diane F Jelinek.

Additional information

This work was supported by National Institutes of Health Grants CA62242 and CA62228

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walters, D., Jelinek, D. A role for Janus kinases in crosstalk between ErbB3 and the interferon-alpha signaling complex in myeloma cells. Oncogene 23, 1197–1205 (2004). https://doi.org/10.1038/sj.onc.1207203

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207203

Keywords

This article is cited by

Search

Advanced search

Quick links