Klein R D, Gu Q, Goddard A, Rosenthal A
Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080-4990, USA.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7108-13. doi: 10.1073/pnas.93.14.7108.
Extracellular proteins play an essential role in the formation, differentiation, and maintenance of multicellular organisms. Despite that, the systematic identification of genes encoding these proteins has not been possible. We describe here a highly efficient method to isolate genes encoding secreted and membrane-bound proteins by using a single-step selection in yeast. Application of this method, termed signal peptide selection, to various tissues yielded 559 clones that appear to encode known or novel extracellular proteins. These include members of the transforming growth factor and epidermal growth factor protein families, endocrine hormones, tyrosine kinase receptors, serine/threonine kinase receptors, seven transmembrane receptors, cell adhesion molecules, extracellular matrix proteins, plasma proteins, and ion channels. The eventual identification of most, or all, extracellular signaling molecules will advance our understanding of fundamental biological processes and our ability to intervene in disease states.
细胞外蛋白在多细胞生物的形成、分化和维持过程中发挥着至关重要的作用。尽管如此，对编码这些蛋白的基因进行系统鉴定仍是不可能的。我们在此描述一种高效方法，通过在酵母中进行一步筛选来分离编码分泌型和膜结合型蛋白的基因。将这种称为信号肽筛选的方法应用于各种组织，得到了559个克隆，这些克隆似乎编码已知或新型的细胞外蛋白。其中包括转化生长因子和表皮生长因子蛋白家族的成员、内分泌激素、酪氨酸激酶受体、丝氨酸/苏氨酸激酶受体、七跨膜受体、细胞粘附分子、细胞外基质蛋白、血浆蛋白和离子通道。最终鉴定出大多数或所有细胞外信号分子将推动我们对基本生物学过程的理解，并提升我们干预疾病状态的能力。
