tailieunhanh - Báo cáo khoa học: Interaction with calmodulin is important for the secretion of thimet oligopeptidase following stimulation

Thimet oligopeptidase (EC ; ) was originally described as a neuropeptide-metabolizing enzyme, highly expressed in the brain, kidneys and neuroendocrine tissue. lacks a typical signal peptide sequence for entry into the secretory pathway and is secreted by cells via an uncon-ventional and unknown mechanism. | Interaction with calmodulin is important for the secretion of thimet oligopeptidase following stimulation Lilian C. Russo1 2 Camila N. Goni1 Leandro M. Castro1 Amanda F. Asega3 Antonio C. M. Camargo3 Cleber A. Trujillo4 Henning Ulrich4 Marc J. Glucksman5 Cristoforo Scavone2 and Emer S. Ferro1 1 Department of CellBiology and Development Institute of BiomedicalSciences University of Sao Paulo Brazil 2 Department of Pharmacology Institute of BiomedicalSciences University of Scio Paulo Brazil 3 Center for Applied Toxinology CAT CEPID Butantan Institute Sao Paulo Brazil 4 Departamento de Bioquimica Instituto de Quimica University of Sao Paulo Brazil 5 Midwest Proteome Center and Department of Biochemistry and Molecular Biology Rosalind Franklin University of Medicine and Science Chicago Medical School North Chicago IL USA Keywords 14-3-3e calmodulin protein kinase A protein-protein interaction unconventional secretion Correspondence E. S. Ferro Laboratorio de Comunicacao Celular Departamento de Biologia Celular e do Desenvolvimento Instituto de Ciencias Biomedicas Universidade de Sao Paulo Av. Prof. Lineu Prestes 1524 Sala 431 Sao Paulo SP 05508-900 Brazil Fax 55 11 3091 7402 Tel 55 11 3091 7310 E-mail eferro@ Received 11 May 2009 revised 3 June 2009 accepted 10 June 2009 doi Thimet oligopeptidase EC was originally described as a neuropeptide-metabolizing enzyme highly expressed in the brain kidneys and neuroendocrine tissue. lacks a typical signal peptide sequence for entry into the secretory pathway and is secreted by cells via an unconventional and unknown mechanism. In this study we identified a novel calcium-dependent interaction between and calmodulin which is important for the stimulated but not constitutive secretion of . We demonstrated that in vitro and calmodulin physically interact only in the presence of Ca2 with an estimated Kd value of pM. Confocal microscopy .