SELECTION FOR GENES ENCODING SECRETED PROTEINS AND RECEPTORS

Extracellular proteins play an essential role in the formation, differ entiation, and maintenance of multicellular organisms. Despite that, t he systematic identification of genes encoding these proteins has not been possible. We describe here a highly efficient method to isolate g enes encoding secreted and membrane-bound proteins by using a single-s tep selection in yeast. Application of this method, termed signal pept ide selection, to various tissues yielded 559 clones that appear to en code known or novel extracellular proteins. These include members of t he transforming growth factor and epidermal growth factor protein fami lies, endocrine hormones, tyrosine kinase receptors, serine/threonine kinase receptors, seven transmembrane receptors, cell adhesion molecul es, extracellular matrix proteins, plasma proteins, and ion channels. The eventual identification of most, or all, extracellular signaling m olecules will advance our understanding of fundamental biological proc esses and our ability to intervene in disease states.