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 a cid (c-di-GMP) on the lymphoblastoid CD4+ Jurkat cell line was studied. Whe n exposed to 50 mu M c-di-GMP, Jurkat cells exhibited a markedly elevated e xpression of the CD4 receptor of up to 6.3-fold over controls. C-di-GMP als o causes blockage of the cell cycle at the S-phase, characterized by increa sed cellular thymidine uptake, reduction in G2/M-phase cells, increase in S -phase cells and decreased cell division. Additionally c-di-GMP naturally e nters these cells and binds irreversibly to the P21(ras) protein. The effec ts described appear to be unique for c-di-GMP. (C) 1999 Federation of Europ ean Biochemical Societies.