Identification of a novel mammalian post-translational modification, phosphocholine, on placental secretory polypeptides.
Placental neurokinin B appears to be post-translationally modified by phosphocholine (PC) attached to the aspartyl side chain at residue 4 of the mature peptide. Corticotrophin releasing factor (CRF) was found to be expressed by the rat placenta with the main secreted forms being phosphocholinated proCRF+/- one or two polysaccharide moieties. A combination of high-pressure liquid chromatography (HPLC) and two-site immunometric analysis suggested that PC was also attached to the placental precursors of adrenocorticotrophin, hemokinin, activin and follistatin. However, the fully processed forms of rat placental activin and CRF were free of PC. Formerly, the parasitic filarial nematodes have used PC as a post-translational modification, attached via the polysaccharide moiety of certain secretory glycoproteins to attenuate the host immune system allowing parasite survival, but it is the PC group itself which endows the carrier with the biological activity. The fact that treatment of proCRF peptides with phospholipase C but not endoglycosidase destroyed PC immunoreactivity suggested a simpler mode of attachment of PC to placental peptides than that used by nematodes. Thus, it is possible that by analogy the placenta uses its secreted phosphocholinated hormones to modulate the mother's immune system and help protect the placenta from rejection.
Lovell
Tristan M
TM
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Woods
Russell J
RJ
Butlin
David J
DJ
Brayley
Kerensa J
KJ
Manyonda
Isaac T
IT
Jarvis
Jackie
J
Howell
Steve
S
Lowry
Philip J
PJ
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D015287:Neurokinin B / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010767:Phosphorylcholine / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D010455:Peptides; D010767:Phosphorylcholine; D015287:Neurokinin B; D003346:Corticotropin-Releasing Hormone