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  • Original Paper
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Cdk9, a member of the cdc2-like family of kinases, binds to gp130, the receptor of the IL-6 family of cytokines

Oncogene volume 21, pages 7464–7470 (2002)Cite this article

Abstract

Cdk9 is a member of the Cdc2-like family of kinases. It binds to members of the family of cyclin T (T1, T2a and T2b) and to cyclin K. The Cdk9/cyclin T complex appears to be involved in regulating several physiological processes. In fact Cdk9 is the kinase of the P-TEFb complex, involved in basal transcription. Cdk9 has also been described as the kinase of the TAK complex, homologous to P-TEFb and involved in HIV replication. Here we show that Cdk9 interacts with gp130, the receptor of the Interleukin-6 (IL-6) family of cytokines, which includes Leukemia Inhibitory Factor (LIF), Oncostatin M (OSM), Ciliary Neurotrophic Factor (CNTF), Interleukin-11 (IL-11) and Cardiotrophin (CT-1). IL-6 is a key regulator of hematopoiesis, immunological responses and inflammation. In addition, IL-6 plays a major role in the endocrine and nervous systems. Signal transduction by gp130 is mediated by physical interaction of the cytoplasmic region of gp130 with cellular kinases and results in the transcriptional activation of cellular and viral genes. We found that Cdk9 interacts in vitro with the cytoplasmic region of gp130 and we succeded in reproducing this interaction in vivo. Cdk9 expression was found both in the nucleus and in the cytoplasm. The binding occurring between Cdk9 and gp130 increased upon IL-6 stimulation. We also observed that Cdk9 synergized with IL-6 in inducing the activation of an IL-6-responsive reporter plasmid. In summary, these results point to a previously undisclosed role for Cdk9 in signal transduction.

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Acknowledgements

We acknowledge G Scala for his contribution the early stage of this work. G De Falco and C Bellan are supported by ‘Dottorato in Patologia Diagnostica Quantitativa’, University of Siena, Italy. This work was supported by grants from the National Institute of Health and the Sbarro Health Research Organization (A Giordano). G De Falco would like to thank Giovanni Sorrentino and LM Neri is grateful to Paola Ziccone for their continuous encouragement, support and understanding. We also thank Alan and Cecilia Bergstein for their support.

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Authors and Affiliations

  1. Sbarro Institute for Cancer Research & Molecular Medicine, College of Science & Technology, Temple University, Philadelphia, 19122, Pennsylvania, PA, USA

    Giulia De Falco, Cristiana Bellan, Lorenzo Leoncini & Antonio Giordano

  2. Istituto di Anatomia e Istologia Patologica, Via delle Scotte, Siena, 6-53100, Italy

    Giulia De Falco & Cristiana Bellan

  3. Dipartimento di Morfologia ed Embriologia, Sezione di Anatomia Umana, Università di Ferrara, via Fossato di Mortara 66, Ferrara, 44100, Italy

    Luca Maria Neri

  4. Istituto di Citomorfologia Normale e Patologica del CNR, c/o IOR, via di Barbiano 1/10, Bologna, 40137, Italy

    Luca Maria Neri

  5. Dipartimento di Biologia Evolutiva e Comparata, Università Federico II di Napoli, Italy

    Maria De Falco

  6. Jefferson Medical College, KCI Room 376, 1020 Locust Street, Pennsylvania, Philadelphia, 19107, PA, USA

    Zailin Yu

  7. Istituto di Anatomia Topografica, Seconda Università di Napoli, Italy

    Antonio De Luca

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  1. Giulia De Falco
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  2. Luca Maria Neri
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  8. Antonio Giordano
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Correspondence to Antonio Giordano.

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Falco, G., Neri, L., Falco, M. et al. Cdk9, a member of the cdc2-like family of kinases, binds to gp130, the receptor of the IL-6 family of cytokines. Oncogene 21, 7464–7470 (2002). https://doi.org/10.1038/sj.onc.1205967

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