The OMgp gene, a second growth suppressor within the NF1 gene

Amyn A. Habib, Jeffrey R. Gulcher, Thorbergur Högnason, Leiya Zheng, Kári Stefánsson

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The Oligodendrocyte-Myelin glycoprotein gene (OMgp) is placed within an intron of the NF1 gene. Neurofibromin, the product of NF1, acts as a RasGAP and suppresses growth; inactivating mutations in NF1 lead to neurofibromatosis type 1. We report that OMgp also has growth suppressive effects and downregulates mitogenic signaling pathways closely related to those influenced by neurofibromin. Overexpression of OMgp alters mitogenic signaling in NIH3T3 fibroblasts. Cells overexpressing OMgp grow more slowly in serum compared to controls and show a partial G1 block upon cell cycle analysis. PDGF is the primary mitogen for fibroblasts in serum. Overexpression of OMgp alters PDGF signaling in fibroblasts which results in a block of mitogenic signaling. PDGF induced activation of c-Src is blocked, as is the induction of c-Myc and c-Fos, while tyrosine phosphorylation of the PDGFβ receptor, PLCγ1 and induction of c-Jun are intact. Although a number of genes embedded within other genes have been described, the biological significance of this arrangement remains unknown. We demonstrate here that structurally unrelated products of two such genes may exercise closely related functions. Our data also raise the possibility of a role for OMgp in disorders of cell proliferation such as NF1.

Original languageEnglish (US)
Pages (from-to)1525-1531
Number of pages7
JournalOncogene
Volume16
Issue number12
DOIs
StatePublished - Mar 26 1998

Keywords

  • Growth suppressor
  • NIH3T3 fibroblasts
  • Neurofibromin
  • OMgp
  • Oligodendrocyte-Myelin glycoprotein
  • PDGF signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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