Prosaptide activates the MAPK pathway by a G-protein-dependent mechanism essential for enhanced sulfatide synthesis by Schwann cells
- 1 March 1998
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 12 (3), 307-314
- https://doi.org/10.1096/fasebj.12.3.307
Abstract
Prosaposin, the precursor of saposins A, B, C, and D, was recently reported to be a neurotrophic factor in vivo and in vitro. The neurotrophic region of prosaposin has been localized to a 12-amino acid sequence within the saposin C domain and has been used to derive biologically active synthetic peptides (14–22 residues), called prosaptides. Treatment of primary Schwann cells and an immortalized Schwann cell line, iSC, with a 14-mer prosaptide, TX14(A) (10 nM), enhanced phosphorylation of mitogen-activated kinases ERK1 (p44 MAPK) and ERK2 (p42 MAPK) within 5 min, which was blocked by 4 h pretreatment with pertussis toxin. Furthermore, incubation of Schwann cells with the nonhydrolyzable GDP analog GDP-βS inhibited TX14(A)-induced ERK phosphorylation. TX14(A) enhanced the sulfatide content of primary Schwann cells by 2.5-fold, which was inhibited by pretreatment with pertussis toxin or the synthetic MAP kinase kinase inhibitor PD098059. In addition, TX14(A) increased the tyrosine phosphorylation of all three isoforms of the adapter molecule, Shc, which coincided with the association of p60Src and PI(3)K. Inhibition of PI3(K) by wortmannin blocked TX14(A)-induced ERK phosphorylation. These data demonstrate that TX14(A) uses a pertussis toxin-sensitive G-protein pathway to activate ERKs, which is essential for enhanced sulfatide synthesis in Schwann cells.—Campana, W. M., Hiraiwa, M., O'Brien, J. S. Prosaptide activates the MAPK pathway by a G-protein-dependent mechanism essential for enhanced sulfatide synthesis by Schwann cells. FASEB J. 12, 307–314 (1998)Keywords
This publication has 36 references indexed in Scilit:
- Prosaposin Receptor: Evidence for a G-Protein-Associated ReceptorBiochemical and Biophysical Research Communications, 1997
- Role of Extracellular Signal‐Regulated Protein Kinases 1 and 2 in Oligodendroglial Process ExtensionJournal of Neurochemistry, 1997
- Induction of MAPK Phosphorylation by Prosaposin and Prosaptide in PC12 CellsBiochemical and Biophysical Research Communications, 1996
- Role of c-Src Tyrosine Kinase in G Protein-coupled Receptorand Gβγ Subunit-mediated Activation of Mitogen-activated Protein KinasesJournal of Biological Chemistry, 1996
- Phosphatidylinositol 3-Kinase Is an Early Intermediate in the Gβγ-mediated Mitogen-activated Protein Kinase Signaling PathwayPublished by Elsevier BV ,1996
- Functional Organization of Saposin CJournal of Biological Chemistry, 1996
- Ras-Dependent Activation of Fibroblast Mitogen-Activated Protein Kinase by 5-HT1A Receptor via a G Protein βγ-Subunit-Initiated PathwayBiochemistry, 1996
- Protection by Prosaposin Against Ischemia-Induced Learning Disability and Neuronal LossBiochemical and Biophysical Research Communications, 1994
- Sphingolipid activator protein deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: Biochemical signs of combined sphingolipidosesEuropean Journal of Pediatrics, 1989
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970