Habib A A, Gulcher J R, Högnason T, Zheng L, Stefánsson K
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Oncogene. 1998 Mar 26;16(12):1525-31. doi: 10.1038/sj.onc.1201683.
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.
少突胶质细胞-髓磷脂糖蛋白基因（OMgp）位于神经纤维瘤病1型基因（NF1）的一个内含子内。神经纤维瘤蛋白是NF1的产物，作为一种RasGAP发挥作用并抑制生长；NF1的失活突变会导致1型神经纤维瘤病。我们报告OMgp也具有生长抑制作用，并下调与神经纤维瘤蛋白影响的信号通路密切相关的促有丝分裂信号通路。OMgp的过表达会改变NIH3T3成纤维细胞中的促有丝分裂信号。与对照相比，过表达OMgp的细胞在血清中生长更慢，细胞周期分析显示有部分G1期阻滞。血小板衍生生长因子（PDGF）是血清中成纤维细胞的主要促有丝分裂原。OMgp的过表达会改变成纤维细胞中的PDGF信号，导致促有丝分裂信号阻滞。PDGF诱导的c-Src激活被阻断，c-Myc和c-Fos的诱导也被阻断，而PDGFβ受体、磷脂酶Cγ1的酪氨酸磷酸化以及c-Jun的诱导是完整的。虽然已经描述了许多嵌入在其他基因中的基因，但这种排列的生物学意义仍然未知。我们在此证明，两个这样的基因在结构上不相关的产物可能行使密切相关的功能。我们的数据还提出了OMgp在诸如1型神经纤维瘤病等细胞增殖紊乱中发挥作用的可能性。
