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 understood. Its phosphorylation state and activation by Ca2+- and calmodulin-dependent protein kinase (CaMK) II were therefore examined. Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site. Both ATF1 and CREB bound CBP in a phosphorylation-dependent manner. As expected from these in vitro studies, transient transfection studies revealed that ATF1 is activated by CaMK II. Our findings suggest that CaMK II mediates transactivation of cAMP responsive genes via ATF1.
Shimomura
A
A
Department of Anatomy, Nagoya University School of Medicine, Japan.
Ogawa
Y
Y
Kitani
T
T
Fujisawa
H
H
Hagiwara
M
M
D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D012694:Serine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases