Induction of NGFI-B gene expression during T cell activation. Role of protein phosphatases.

mRNA expression of the immediate-early gene NGFI-B was investigated in T cells during the G0/G1 transition as well as throughout the G1 phase. After stimulation of T lymphocytes with Con A or phorbol 12,13 dibutyrate (PDBu), NGFI-B gene expression showed an induction of at least sevenfold within 3 h of stimulation. Twenty-four h later, however, the level of NGFI-B transcripts had fallen to almost basal levels. Activation of the Ca2+ signaling pathway also produced an induction of this gene, although to a lesser extent than the one obtained after protein kinase C activation. Similar transient kinetics of NGFI-B mRNA were also observed after PDBu stimulation of G1 lymphoblasts. However, the induction of NGFI-B by IL-2 is dependent on the presence of cycloheximide. Con A-induced activation of NGFI-B gene expression was not overcome by cyclosporin A or by 8Br-cAMP, but was partially prevented by dexamethasone. In lymphoblasts, okadaic acid caused the induction of NGFI-B gene expression, indicating a role for the serine/threonine protein phosphatases PP1 and PP2A in the regulation of this gene in resting cells. Okadaic acid-induced NGFI-B transcripts were significantly more stable than PDBu-induced NGFI-B mRNA. Thus, the level of NGFI-B transcripts in T cells might be determined by the balance between the activities of several serine/threonine protein kinases and phosphatases. Together, these findings indicate that the transient induction of NGFI-B transcripts is associated with normal lymphocyte activation. Because the mRNA for NGFI-B codes for a zinc-finger DNA-binding protein, these results suggest that NGFI-B participates in transcriptional regulation during T cell activation.