Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction

Intercellular communication in multicellular organisms requires the relay of extracellular signals by cell surface proteins to the interiors of cells. The availability of genome sequences from humans and several model organisms has facilitated the identification of several human plasma membrane receptor families and allowed the analysis of their phylogeny. This review provides a global categorization of most known signal transduction-associated receptors as enzymes, recruiters, and latent transcription factors. The evolution of known families of human plasma membrane signaling receptors was traced in current literature and validated by sequence relatedness. This global analysis reveals themes that recur during receptor evolution and allows the formulation of hypotheses for the origins of receptors. The human receptor families involved in signaling (with the exception of channels) are presented in the Human Plasma Membrane Receptome database. Receptor proteins in the plasma membrane of cells are responsible for the reception and transmission of outside signals secreted by neighboring or remote cells. Defects in these cell surface proteins are responsible for various hormonal diseases, developmental defects, and tumor formation. Based on functional similarity and sequence relatedness, human receptor genes can be grouped into a limited number of families, and their evolutionary origins can now be traced by comparing sequences of similar genes found in humans and various model organisms. This STKE Review discusses the common features and possible evolutionary origins of some of the human plasma membrane receptors involved in signal transduction. The Review contains nine figures, two tables, and 157 citations. A database (http://Receptome.Stanford.edu) has been established to allow searches for human plasma membrane receptors based on their family relationship, evolution, and sequences.