IDENTIFICATION OF A 2ND RAT PANCREATITIS-ASSOCIATED PROTEIN - MESSENGER-RNA CLONING, GENE STRUCTURE, AND EXPRESSION DURING ACUTE-PANCREATITIS

The pancreatitis-associated protein (PAP) is a lectin-related secretor y protein present in small amounts in the rat pancreas and overexpress ed during the acute phase of pancreatitis. On the other hand, PAP is c onstitutively expressed in the intestinal tract but not in other tissu es. We cloned from a pancreatic cDNA library two overlapping cDNAs enc oding a protein structurally related to PAP. This second PAP, which wa s called PAP II, was the same size as the original PAP (PAP I) and sho wed 74.3% amino acid homology. Studies on gene expression demonstrated that PAP II mRNA concentration increased within 6 h following inducti on of pancreatitis, reached maximal levels (>200 times control values) at 24-48 h, and decreased thereafter, similar to PAP I. However, PAP II mRNA could not be detected in the intestinal tract or in other tiss ues. We also isolated a PAP II genomic DNA fragment which was characte rized over 2.7 kb of gene sequence and 1.9 kb of 5' flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP II mRNA. The PAP II coding sequence spanned six exons separ ated by five introns. Several potential regulatory elements were ident ified in the promoter region, including two glucocorticoid-response el ements and one IL-6-response element. Antibodies raised to a synthetic peptide of PAP II detected a single band in Western blot analysis of the pancreatic secretory proteins from rats with pancreatitis, with a M(r) compatible with the theoretical M(r) of PAP II. PAP I and PAP II are members of a new family of pancreatic secretory proteins, structur ally related to C-type lectins, that might be classified among the acu te-phase proteins.