A NEW PROLINE-RICH PROTEIN-PRECURSOR EXPRESSED IN THE SALIVARY-GLANDSOF THE RAT IS ENCODED BY A GENE HOMOLOGOUS TO THE GENE CODING FOR THEPROHORMONE-LIKE PROTEIN SMR1

A gene encoding a prohormone-like protein, (SMR1) has previously been characterized and shown to be expressed in the rat submandibular gland s under androgenic control (Rosinski-Chupin, I., Tronik, D., and Rouge on, F. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8553-8557). This gen e, now named VCS-alpha1, belongs to a multigene family (Rosinski-Chupi n, I., and Rougeon, F. (1990) DNA Cell Biol. 9, 553-559). We now descr ibe the structure and the expression of a second member (VCS-beta1) of this family. The two genes differ principally in the protein-coding r egion, therefore we have named these related genes VCS (variable codin g sequence). Genomic clones containing the VCS-beta1 gene were obtaine d by screening a lambdaEMBL3 library with a probe corresponding to the VCS-alpha1 cDNA. The nucleotide sequence of VCS-beta1 predicted a str ucture containing three exons. This structure, confirmed by sequencing a BCS-beta1 cDNA obtained by reverse polymerase chain reaction, is id entical to the organization of the VCS-alpha1 gene. Comparison of the VCS-beta1 and VCS-alpha1 genomic sequences indicates regions of hemolo gy which are unevenly distributed, suggesting a differential evolution of some areas (particularly the third exon) of the VCS genes. The VCS -beta1 cDNA codes for a proline-rich protein precursor named PR-Vbeta1 (148 amino acids, 39.2% proline, 10.8% glycine) and characterized by a secretory signal-peptide and three repeats of a unit rich in proline residues surrounded by two clusters of potential endoprotease cleavag e sites. mRNA coding for PR-Vbeta1 was detected in the submandibular-s ublingual gland complex of male and female rats. PR-Vbeta1 is homologo us to the proline-rich peptide B isolated from human saliva (Isemura, S., Saitoh, E., and Sanada, K. (1979) J. Biochem. (Tokyo) 86, 79-86) a nd to the submandibular proline-rich protein precursor MSG1 of the mou se (D. Tronik-Le Roux, M. Senorale-Pose, and F. Rougeon, manuscript in preparation). Our observations provide evidence that in addition to t he known proline-rich protein genes, there is, in rodent and probably human genomes, another class of genes coding for salivary proline-rich proteins. The high conservation of various sites for bacterial collag enases localized in the repeat region of PR-Vbeta1, MSG1, and PRP-B su ggest a protective function of these proteins in the oral cavity.