A new calmodulin-binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation

© The Authors Journal compilation © 2014 Biochemical Society. IP3-3K [Ins(1,4,5)P33-kinase] is a key enzyme that catalyses the synthesis of Ins(1,3,4,5)P4, using Ins(1,4,5)P3and ATP as substrates. Both inositides, substrate and product, present crucial roles in the cell. Ins(1,4,5)P3is a key point in Ca2+metabolism that promotes Ca2+release from intracellular stores and together with Ins(1,3,4,5)P4regulates Ca2+homoeostasis. In addition, Ins(1,3,4,5)P4is involved in immune cell development. It has been proved that Ca2+/CaM (calmodulin) regulates the activity of IP3-3K, via direct interaction between both enzymes. Although we have extensive structural knowledge of the kinase domains of the three IP3-3K isoforms, no structural information is available about the interaction between IP3-3K and Ca2+/CaM. In the present paper we describe the crystal structure of the complex between human Ca2+/CaM and the CaM-binding region of human IP3-3K isoform A (residues 158-183) and propose a model for a complex including the kinase domain. The structure obtained allowed us to identify all of the key residues involved in the interaction, which have been evaluated by site-directed mutagenesis, pull-down and fluorescence anisotropy experiments. The results allowed the identification of a new CaM-binding motif, expanding our knowledge about how CaM interacts with its partners.Peer Reviewe

Impacts of Aggregation on Relative Performances of Nonsurvey Updating Techniques And Intertemporal Stability of Input–Output Coefficients

In many instances, and for variety of reasons, input–output researchers are compelled to both employ mechanical techniques to update older survey-based tables as well as using more aggregated ones. This combination, however, gives rise to several concerns. The present paper is an attempt to investigate two such questions. First, the effects of aggregation on the accuracy ranking of selected updating methods, and second, the effects of aggregation on intertemporal stability of the input–output coefficients. To probe these issues, three updating methods were selected. These methods are NAÏVE or constant coefficient hypothesis, RAS or biproportional method, and LaGrangian optimization technique. Two survey-based tables from the former Soviet Union along with the selected updating techniques are used to generate updated target year’s direct and inverse transaction matrices at four aggregation levels. Comparison of the resultant estimates at these four levels of aggregation with their counterparts in the actual benchmark table reveals that a higher level of aggregation neither affects the rankings of the updating methods nor does it universally and unequivocally leads to a higher degree of intertemporal stability of input–output coefficients. Copyright Springer Science+Business Media, Inc. 2005aggregation, input–output coefficients, intertemporal stability of coefficients, LaGrangian, RAS, updating methods,