Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells.
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.
Sivertsen
Einar A
EA
Department of Immunology, Institute of Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway.
Huse
Kanutte
K
Hystad
Marit E
ME
Kersten
Christian
C
Smeland
Erlend B
EB
Myklebust
June H
JH
D055418:Bone Morphogenetic Protein 6; D052004:Bone Morphogenetic Protein Receptors / Q000096:biosynthesis / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D018390:Gene Targeting; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology
C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D006131:Growth Inhibitors; D052004:Bone Morphogenetic Protein Receptors