title: Cdk9, a member of the cdc2-like family of kinases, binds to gp130, the receptor of the IL-6 family of cytokines.
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.
authors.affiliation: Sbarro Institute for Cancer Research & Molecular Medicine, College of Science & Technology, Temple University, Philadelphia, Pennsylvania, PA 19122, USA.
authors.forename: Giulia De
authors.initials: GD
authors.lastname: Falco
authors.forename: Luca Maria
authors.initials: LM
authors.lastname: Neri
authors.forename: Maria De
authors.initials: MD
authors.lastname: Falco
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Zailin
authors.initials: Z
authors.lastname: Yu
authors.forename: Antonio De
authors.initials: AD
authors.lastname: Luca
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics; D010957:Plasmids; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050822:Cytokine Receptor gp130; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases