15.1 Introduction Signal transduction at the cellular level refers to the movement of signals from outside the cell to the inside. The movement of signals can be simple, like that as- sociated with receptor molecules of the acetylcholine class. Complex signal trans- duction involves the coupling of ligand–receptor interactions to intracellular events. These events include phosphorylations by tyrosine kinases and/or serine/ threonine kinases or ligand activated gene expression. The eventual outcome is an alteration in cellular activity and changes in the program of genes expressed with- in the responding cells. Signal transducing receptors can be divided into four general classes: · Receptors that penetrate the plasma membrane and have intrinsic enzymatic ac- tivity, including tyrosine kinases (e.g. receptors for PDGF, insulin, EGF, and FGF), tyrosine phosphatases (e.g. CD45 protein of T cells and macrophages), guanylate cyclases and serine/threonine kinases (e.g. activin and TGF recep- tors). Receptors with intrinsic tyrosine kinase activity either are capable of au- tophosphorylation as well as phosphorylation of other substrates or are coupled to intracellular tyrosine kinases by direct protein–protein interactions. · Receptors that are coupled, inside the cell, to GTP binding and hydrolyzing pro- teins (termed G-proteins). Receptors of this class all have a structure of seven transmembrane spanning domains and are also known as serpentine receptors. Examples are the adrenergic receptors, odorant receptors, and certain hormone receptors (e.g. for glucagon, angiotensin, and vasopressin). · Receptors that are found intracellularly and upon ligand binding migrate to the nucleus where the ligand–receptor complex directly affects gene transcription. · Intracellular ligand activated receptors which are mainly localized in the nuclear compartment and whose cellular localization is independent of ligand-bound status. Signaling pathways pertaining to the latter receptors will be the focus of this arti- cle. 267 15 Cross-talk between Intracellular Lipid Binding Proteins and Ligand Activated Nuclear Receptors – A Signaling Pathway for Fatty Acids Christian Wolfrum and Friedrich Spener Cellular Proteins and their Fatty Acids in Health and Disease. Edited by Asim K. Duttaroy, Friedrich Spener Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30437-1