The tetradecapeptide
hormone somatostatin arises from proteolytic processing of a large precursor, pre-
prosomatostatin. Studies of other
hormone precursors predict that the NH2 terminus of pre-
prosomatostatin comprises a leader, or signal, region which is cleaved during its translation. Such co-translational cleavage would generate
prosomatostatin. In these studies, we present the complete sequence of rat pre-
prosomatostatin, deduced from the nucleotide sequence of cDNAs derived from a
somatostatin-rich medullary
thyroid carcinoma. These findings indicate that rat pre-
prosomatostatin contains 116
amino acids (12,737 daltons). Cell-free translations of medullary
thyroid carcinoma mRNA with dog pancreas microsomal membranes were performed to identify the cleavage point of the leader region from
prosomatostatin. Partial microsequencing data indicates that the cleavage occurs between the
glycine and
alanine at positions 24 and 25 of pre-
prosomatostatin. Thus, rat
prosomatostatin contains 92
amino acids (10,388 daltons). Comparison of the amino acid sequences of the rat and human pre-prosomatostatins reveals only four amino acid substitutions. In view of the high degree of homology between rat and human pre-
prosomatostatin, we expect a similar cleavage site and NH2-terminal structure for human
prosomatostatin. The high level of conservation between rodents and humans of the entire pre-
prosomatostatin molecule further suggests the possibility of
biologic functions of the NH2-terminal portions of
prosomatostatin.