説明
Publisher Summary The stimulated genes have a common promoter element, the CAMP response element (CRE), which is recognized by a specific binding protein, CREB. The binding of CREB to CRE does not itself induce transcription, because this requires phosphorylation of CREB at Ser133. In the nervous system, signals transmitted across synapses are known to regulate gene expression in the postsynaptic cell. This process often involves membrane depolarization and subsequent elevation of intracellular Ca 2+ . Phosphorylation of Ser133 stimulates the ability of CREB to activate gene transcription, suggesting that CREB may mediate transcriptional induction by Ca 2+ as well as by CAMP. Two types of Ca 2+ /calmodium-dependent protein kinases, CaM kinase II and CaM kinase N, are able to phosphorylate CREB at Ser133. Immunocytochemical studies with antisera to CaM kinase II and CaM kinase IV revealed that both are expressed in the GCL and in the inner nuclear layer (INL). CaM kinase II, however, is localized in the inner border of the INL, whereas CaM kinase IV is distributed in the outer half of the INL. There is no clue as to whether Ca 2+ /calmodulin-dependent (type I) adenylyl cyclase is involved in Ca 2+ induction of CREB pathway. The nuclear localization of CaM kinase IV and an isoform (δb) of CaM kinase II provide support for the idea that Ca 2+ /calmodulin-dependent protein kinases directly phosphorylate Ser133 of CREB and thus activate transcription.