Identification of a molluscan homologue of the neuroendocrine polypeptide 7B2.
In vertebrates, interaction of prohormone convertase 2 (PC2) with the highly conserved polypeptide 7B2 is essential for transport and maturation of proPC2 in the regulated secretory pathway. In vitro, 7B2 displays a strong inhibitory activity toward PC2. Here, we characterize a cDNA encoding the first invertebrate 7B2-related protein (L7B2) from the brain of the mollusc Lymnaea stagnalis. The overall amino acid sequence identity between L7B2 and its vertebrate counterparts is surprisingly low (29%) and is restricted to a few small stretches of amino acid residues. Of particular interest are a conserved proline-rich region in the middle portion of the L7B2 sequence and a repeated conserved region in the carboxyl-terminal domain. Synthetic peptides corresponding to the carboxyl-terminal regions inhibit Lymnaea PC2 enzyme activity in extracts of insulin-producing neurons, in which both L7B2 and Lymnaea PC2 are abundantly expressed. Moreover, the peptides inhibit mouse PC2 enzyme activity. Our cloning of invertebrate 7B2 helps to delineate residues that are important for 7B2-PC2 interaction.
Spijker
S
S
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
Smit
A B
AB
Martens
G J
GJ
Geraerts
W P
WP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017124:Conserved Sequence; D018076:DNA, Complementary; D008195:Lymnaea; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones / Q000235:genetics*; D045706:Proprotein Convertase 2; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000037:antagonists & inhibitors
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D013381:Subtilisins; D045706:Proprotein Convertase 2