Insulin receptor dynamics by a novel dominat-negative recombinant receptor

GIUDICE JIMENA; ARNDT-JOVIN DONNA; JOVIN THOMAS M; COLUCCIO LESKOW FEDERICO; JARES-ERIJMAN ELIZABETH

Los Cocos. Córdoba- Argentina

Congreso; THE FIRST SOUTH AMERICAN SPRING SYMPOSIUM IN SIGNAL TRANSDUCTION AND MOLECULAR MEDICINE.; 2010

Insulin regulates different cellular processes such as transport and metabolism of glucose, lipids and proteins, nucleic acid synthesis and gene expression. Two splice variants of IR exist in mammals: IR-A lacking exon 11, and the full length IR-B. Both isoforms behave differently in the presence of ligands and cannot be distinguished by antibodies. While IR-A is expressed during development and has been shown to be missregulated in certain cancers, IR-B is expressed predominantly in metabolic tissues. The insertion of an ACP-tag in the extracellular domain of IR allowed us to label it in the membrane in living cells with small dyes and quantum dots. Recombinant receptor IR-B-A1x3 behaved as a dominant negative, binding insulin but not being capable of activating downstream signaling. This dominant negative IR (dn-IR) permits us to study the differential IR isoform dynamics and to gain insight into the controversial existence of heterodimers IR-A/IR-B in a new way.