THE SMALL PROLINE-RICH PROTEINS CONSTITUTE A MULTIGENE FAMILY OF DIFFERENTIALLY REGULATED CORNIFIED CELL-ENVELOPE PRECURSOR PROTEINS

Loricrin, involucrin, small proline-rich protein (SPRR)1, SPRR2, and S PRR3 genes are located within a cluster of 1.5 Mbp on chromosome 1q21 and most likely evolved from a common ancestor. Mono-specific polyclon al antibodies and cDNA probes were produced to investigate SPRR transc ripts and proteins. SPRR expression was restricted to terminally diffe rentiating squamous cells, preferentially located at the cell peripher y, and immunoreactivity was greatly reduced in cells with a mature cor nified cell envelope. Furthermore, detectable SPRR2 and SPRR3 levels w ere strongly increased in differentiating keratinocyte cultures after addition of LTB-2, a specific inhibitor of transglutaminases, suggesti ng that they are precursor proteins of the cornified cell envelope. In normal epidermis, SPRR1 was restricted to appendageal areas, SPRR2 wa s expressed coherentry, and SPRR3 was completely absent. In the upper digestive tract, SPRR1 was expressed in sublingual and tongue epitheli um, SPRR2 was mostly restricted to lingual papillae, and SPRR3 was abu ndant in oral and esophageal epithelium. In psoriatic epidermis, SPRR1 and SPRR2 were expressed at much higher levels than in normal epiderm is. Addition of 10(-7) M retinoic acid to cultured differentiating ker atinocytes significantly down-regulated the expression of SPRR2 and SP RR3 transcripts and slightly decreased that of SPRR1. Thus, SPRR1 SPRR 2, and SPRR3 are differentially expressed in vivo and in vitro, sugges ting that the SPRR multigene family evolved to serve as highly special ized cornified cell envelope precursor proteins in stratified epitheli a.