CALMODULIN-DEPENDENT PROTEIN-KINASE-II POTENTIATES TRANSCRIPTIONAL ACTIVATION THROUGH ACTIVATING TRANSCRIPTION FACTOR-1 BUT NOT CAMP RESPONSE ELEMENT-BINDING PROTEIN

Activating transcription factor 1 (ATF1) and the cAMP response element binding protein (CREB) are members of the CREB/ATF family implicated in cAMP- and calcium-induced transcriptional activation, Although ATF1 and CREB share extensive homology, the function of ATF1 is poorly und erstood, Its phosphorylation state and activation by Ca2+- and calmodu lin dependent protein kinase (CaMK) II were therefore examined, Phosph opeptide mapping analysis and Western blotting studies demonstrated th at in vitro, CaMK II phosphorylates only Ser(63) (corresponding to Ser (133) of CREB), which is essential for the activation, and not Ser(72) (corresponding to Ser(142) Of CREB), which is a negative regulation s ite. Both ATF1 and CREB bound CBP in a phospho rylation-dependent mann er, As expected from these in vitro studies, transient transfection st udies revealed that ATF1 is activated by CaMK II, Our findings suggest that CaMK II mediates transactivation of cAMP responsive genes via AT F1.