ACTIVATION PROTEIN 1-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF INTERLEUKIN-2 GENE BY CA2+ CALMODULIN KINASE TYPE IV/GR/

The Ca2+/calmodulin-dependent protein kinase (CaMK) type IV/Gr is sele ctively expressed in T lymphocytes and is activated after signaling vi a the T cell antigen receptor (TCR), indicating that it mediates some of the Ca2+-dependent transcriptional events that follow TCR engagemen t. Here we show that CaMKIV/Gr induces the transcription factor activa tion protein 1 (AP-1) alone or in synergy with T cell mitogens and wit h the p21(ras) oncoprotein. CaMKIV/Gr signaling is associated with tra nscriptional activation of c-fos but is independent of p21(ras) or cal cineurin. AP-1 is an integral component of the nuclear factor of activ ated T cells (NFAT) transcriptional complex, which is required for int erleukin 2 gene expression in T cells. We demonstrate that CaMKIV/Gr r econstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non-T cells. These results reveal a central role for CaMKIV/Gr as a Ca2+-regulated activator of gene trans cription in T lymphocytes.