Ca 2+ /CaM protein kinases (CaM-K) have significant roles for Ca 2+ -dependent signal transduction. CaM-K-mediated signal cascade consists of the upstream CaM-kinase kinase (CaM-KK) and downstream CaM kinase I (CaM-KI) and CaM-kinase IV (CaM-KIV). A transcription factor cAMP-responsive element binding protein (CREB) is known to be activated by phosphorylation with downstream CaM-KIV. In this study, we identified C. elegans orthologues of mammalian CaM-KK (
ckk-1 ), CaM-KI (
cmk-1 ) and CREB, and found that CaM-KK-CaM-KI-CREB cascade is conserved and operated both in vitro and in transfected cells. Furthermore, we investigated the physiological functions through this signal cascade by genetical approaches. The distribution of activated CREB was analyzed by using the transgenic worms that carries 4XCRE::gfp fusion gene. GFP fluorescence cannot be seen in normal development, however, transgenic worms carrying constitutive-active form of
cmk-1 induces GFP-expression in small number of sensory neurons in head and tail. On the other hand, wild type and mutant
cmk-1 at T179A did not show any CREB activation, suggesting the requirement of Ca 2+ mobilization and the upstream kinase which was identified as CaM-KK . In addition, CREB-deficeient worms show no GFP fluorescence reasonably. Interestingly, when the worms were maintained in starved condition, the number of GFP-positive neurons increased and the intensity of GFP fluorescence was dramatically enhanced. These results suggest that CaM-KK-CaM-KI-CREB cascade of C. elegans is conserved in vivo in the some sensory neurons and activated by the circumstantial stimuli.