Mannose 6-phosphate-containing peptides activate phospholipase C in proximal tubular basolateral membranes from canine kidney.
To ascertain whether mannose 6-phosphate-containing peptides that bind to the insulin-like growth factor II (IGF II)/mannose 6-phosphate receptor activate phospholipase C, we determined the effect of proliferin, transforming growth factor-beta 1 (TGF-beta 1) precursor, and beta-galactosidase on production of inositol trisphosphate (Ins-P3) in basolateral membranes isolated from the renal proximal tubule of dogs. Both proliferin and TGF-beta 1 precursor stimulated Ins-P3 production in a concentration-dependent manner. Maximal production was stimulated by approximately 10(-13) M of each peptide. beta-Galactosidase had no effect on Ins-P3 generation. Neither proliferin nor TGF-beta 1 precursor potentiated IGF II-stimulated Ins-P3 production. Mannose 6-phosphate itself had no effect on Ins-P3 generation. However, mannose 6-phosphate potentiated production stimulated by 10(-11) M proliferin or 10(-11) M TGF-beta 1 precursor while inhibiting production stimulated by 10(-14) M of either peptide. Addition of anti-mannose 6-phosphate receptor antibodies to basolateral membranes abolished proliferin and TGF-beta 1 precursor-stimulated Ins-P3 generation. We conclude that, in addition to IGF II, mannose 6-phosphate-containing ligands for the IGF II/mannose 6-phosphate receptor activate basolateral membrane phospholipase C. Such activation could reflect a common mechanism for signal transduction by these peptides mediated via the IGF II/mannose 6-phosphate receptor.
Rogers
S A
SA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Purchio
A F
AF
Hammerman
M R
MR
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D005696:Galactosidases / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008360:Mannosephosphates / Q000494:pharmacology; D011388:Prolactin; D011498:Protein Precursors; D011506:Proteins / Q000494:pharmacology*; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*; D001616:beta-Galactosidase / Q000494:pharmacology*
D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008360:Mannosephosphates; C000634106:Prl2c2 protein, mouse; D011498:Protein Precursors; D011506:Proteins; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D016212:Transforming Growth Factor beta; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II; D015291:Transforming Growth Factors; D015544:Inositol 1,4,5-Trisphosphate; D011388:Prolactin; D013006:Growth Hormone; D010738:Type C Phospholipases; D005696:Galactosidases; D001616:beta-Galactosidase