Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3',5'-cyclic diguanylic acid.
The effect of the novel, naturally occurring nucleotide cyclic diguanylic acid (c-di-GMP) on the lymphoblastoid CD4+ Jurkat cell line was studied. When exposed to 50 microM c-di-GMP, Jurkat cells exhibited a markedly elevated expression of the CD4 receptor of up to 6.3-fold over controls. C-di-GMP also causes blockage of the cell cycle at the S-phase, characterized by increased cellular thymidine uptake, reduction in G2/M-phase cells, increase in S-phase cells and decreased cell division. Additionally c-di-GMP naturally enters these cells and binds irreversibly to the P21ras protein. The effects described appear to be unique for c-di-GMP.
Molecular Oncology Laboratory, Rambam Medical Center and Rappaport Institute of Medical Sciences, Haifa, Israel.
O
O
Steinberger
Z
Z
Lapidot
Z
Z
Ben-Ishai
D
D
Amikam
D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability; D048429:Cell Size / Q000187:drug effects; D002855:Chromatography, Thin Layer; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D015704:CD4 Antigens; D006150:Guanine Nucleotides; C062025:bis(3',5')-cyclic diguanylic acid; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D015689:Oncogene Protein p21(ras); D006152:Cyclic GMP; D013936:Thymidine