CAMK4, Active

CAMK4 belongs to the serine/threonine protein kinase family and Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution. Sikela et al. identified that brain CaM kinase IV (CAMK4) appeared to be restricted to brain in the rat; interestingly, it was not detected in the brain of the newborn, but became detectable within a few days after birth. They also raised the possibility that a defect in Camk4 may be responsible for 1 of the mutant phenotypes in the centromeric region near 2 mutations, which known to affect neurologic function and fertility (1). Wei et al. found Camk4-labeled neurons in the hippocampus, amygdala, anterior cingulate cortex, somatosensory cortex, and insular cortex (2). Kang et al. generated transgenic mice in which the expression of a dominant-negative form of Camk4 was restricted to the postnatal forebrain. In these transgenic mice, activity-induced Creb phosphorylation and Fos expression were significantly attenuated. The results indicated that neural activity-dependent CAMK4 signaling in the neuronal nucleus plays an important role in the consolidation/retention of hippocampus-dependent long-term memory (3). Wu et al. generated transgenic mice that selectively express in skeletal muscle a constitutively active form of CAMK4 and concluded that a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells (4). Wei et al. studied pain and fear memory in Camk4-null mice and concluded that Camk4 is crucial in the trapping of Ca2(+)/calmodulin complexes in neuronal nuclei and in Creb phosphorylation and activation (5).