title: A novel calmodulin-β-PIX interaction and its implication in receptor tyrosine kinase regulation.
abstract: Calmodulin (CaM), a ubiquitous calcium-binding protein, regulates numerous cellular processes, primarily in response to calcium flux. We have identified and characterized a novel interaction between CaM and β-p21-activated kinase interacting exchange factor (β-PIX), a putative guanine exchange factor implicated in cell signaling, using affinity pull-down assays, co-immunoprecipitation, co-localization and circular dichroism studies. Fluorescence-based titration and isothermal titration calorimetry experiments revealed a Ca(2+)-dependent binding mechanism (K(D)≤10μM). Further, we show that CaM participates in a multi-protein complex involving β-PIX and E3 ubiquitin ligase c-Cbl (casitas B-cell lymphoma), which may play a critical role in receptor tyrosine kinase regulation and downstream signaling.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Kim
authors.initials: K
authors.lastname: Munro
authors.forename: Zongchao
authors.initials: Z
authors.lastname: Jia
mesh_terms: D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: C576606:ARHGEF7 protein, human; D002147:Calmodulin; D064067:Rho Guanine Nucleotide Exchange Factors; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium