The complexification of cell to cell interactions along metazoan evolution has led to the development of a molecular network specialized in intercellular communication. Receptor tyrosine kinases (RTKs) are among the most ancient and important proteins that emerged in multicellular organisms. RTKs form a superfamily of transmembrane receptors that bind a large panel of ligands including hormones, growth factors and cytokines, and trigger different signalling cascades inside the cell for the control and regulation of key cellular processes. In eumetazoan organisms, RTK mediation is essential for embryogenesis [1,2], growth [3] and metabolic regulations [4]. RTK diversity increased along with speciation, possibly due to the acquisition of new regulatory processes in cell function, so that conserved and original classes of RTK could be found in different metazoan organisms [5][6][7]. RTKs possess a unique transmembrane domain and their capacity to transduce signals inside the cell is dependent on their autophosphorylation and requires vicinity of two tyrosine kinase (TK) domains. Members of the insulin receptor (IR) family belong to the very well conserved RTK class II, and were probably present in the most ancient metazoans because they have been identified in diploblastic organisms like sponge [8]. Although most of the RTK are monomeric and dimerize upon ligand binding, IR are constitutively assembled in a 2 b 2 heterotetramers [9,10]. Binding of insulin peptides