The OMgp gene, a second growth suppressor within the NF1 gene.
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 PDGFbeta receptor, PLCgamma1 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.
Habib
A A
AA
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Gulcher
J R
JR
Högnason
T
T
Zheng
L
L
Stefánsson
K
K
D016475:3T3 Cells; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004789:Enzyme Activation; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early / Q000235:genetics; D016514:Genes, Neurofibromatosis 1; D006131:Growth Inhibitors / Q000235:genetics*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000096:biosynthesis / Q000235:genetics*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D025542:Neurofibromin 1; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; C560529:Omg protein, mouse; D011506:Proteins; D014443:Tyrosine; C099852:PDGF receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases