Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

Eur J Immunol. 2007 Oct;37(10):2937-48. doi: 10.1002/eji.200636759.

Abstract

Bone morphogenetic proteins (BMP) are multifunctional cytokines that belong to the TGF-beta superfamily. BMP have been shown to regulate haematopoietic stem cells, B lymphopoiesis and early thymocyte differentiation. In the present study we explored the role of BMP-6 in Jurkat TAg cells. BMP-6 rapidly induced phosphorylation of Smad1/5/8, p38 and ERK1/2, followed by a potent up-regulation of ID1, ID2 and ID3. ID1 and ID3 were also induced at the protein level. Genome-wide expression profiling of cells treated with BMP-6 compared to medium confirmed that ID1-ID3 were target genes of BMP-6 together with Noggin and Smad6. Furthermore, several genes involved in transcriptional regulation were also identified, including NFKBIA, HEY1, DLX2, KLF10 and early growth response 1. Stimulation with BMP-6 exerted an antiproliferative effect that was counteracted by inhibitor of DNA binding (Id)1 siRNA, indicating that Id1 is an important downstream mediator in Jurkat TAg cells. A subset of CD4(+) T cells were found to express the BMP receptors Alk-2 and Alk-3 (type I), in addition to BMPRII (type II). BMP-6 also induced phosphorylation of Smad1/5/8, followed by transcriptional increase in ID1-ID3 mRNA expression. However, we did not observe significant changes in Id protein expression in CD4(+) T cells. Altogether, the data indicate a role for BMP-6 in human T lineage cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein Receptors / biosynthesis
  • Bone Morphogenetic Protein Receptors / genetics
  • Bone Morphogenetic Proteins / physiology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic / immunology*
  • Gene Targeting
  • Growth Inhibitors / physiology*
  • Humans
  • Jurkat Cells
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Signal Transduction / immunology

Substances

  • BMP6 protein, human
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • Growth Inhibitors
  • Bone Morphogenetic Protein Receptors