7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway.
The neuroendocrine polypeptide 7B2 is a highly conserved secretory protein selectively present in prohormone-producing cells equipped with a regulated secretory pathway. We find that the amino-terminal half of 7B2 is distantly related to chaperonins, a subclass of molecular chaperones. When incubated in vitro with newly synthesized pituitary proteins, recombinant 7B2 specifically associates with prohormone convertase PC2. Metabolic cell labeling combined with coimmunoprecipitation studies showed that, in vivo, the precursor form of 7B2 interacts with the proform of PC2. Pulse-chase analysis revealed that this association is transient in that it commences early in the secretory pathway, while dissociation in the later stages appears to coincide with the cleavages of 7B2, proPC2, and prohormone. Our results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated secretory pathway.
Braks
J A
JA
Department of Animal Physiology, University of Nijmegen, The Netherlands.
Martens
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D018833:Chaperonins; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009490:Neurosecretory Systems / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D045706:Proprotein Convertase 2; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D011498:Protein Precursors; D011506:Proteins; D011994:Recombinant Proteins; C497678:SCG5 protein, human; D011333:Pro-Opiomelanocortin; D013381:Subtilisins; D045706:Proprotein Convertase 2; D018833:Chaperonins