Ras-GTP regulation is not altered in cultured melanocytes with reduced levels of neurofibromin derived from patients with neurofibromatosis 1 (NF1).
Ras-GTP regulation is not altered in cultured melanocytes with reduced levels of neurofibromin derived from patients with neurofibromatosis 1 (NF1).
复制标题
在来自神经纤维瘤病 1 (NF1) 患者的神经纤维蛋白水平降低的培养黑素细胞中，Ras-GTP 调节并未改变。
DOI：
10.1515/bchm3.1995.376.2.91
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
W. Krone
中科院分区：
文献类型：
--
作者：
J. Griesser;D. Kaufmann;I. Eisenbarth;C. Bäuerle;W. Krone
表皮黑素细胞作为神经脊的衍生体，临床上可能受到NF1基因缺陷的影响。NF1基因与p120 GTP酶激活蛋白(p120-GAP)序列同源，神经纤维蛋白被证明参与RAS调节。免疫沉淀法和免疫印迹法检测到NF1患者正常皮肤和咖啡豆黄斑黑素细胞中有神经纤维蛋白的表达，但神经纤维蛋白条带的表达强度低于对照培养物。NF1来源的黑素细胞培养的RAS-GTP/RAS-GDP比值与健康供者来源的Ras-GTP/RAS-GDP比值相当。此外，与对照组相比，NF1黑素细胞培养中细胞裂解产物的总GAP活性没有改变。然而，来自NF1患者和健康捐赠者的增殖黑素细胞的裂解产物显示出比生长不良的细胞高约2倍的GAP活性。在对照组和NF1黑素细胞中，神经纤维素贡献了大约三分之一的GAP活性，这表明它不是这些细胞中RAS的主要调节因子。这些结果表明，神经纤维蛋白在黑素细胞中的功能并不局限于调节RAS活性。
As derivatives of the neural crest, epidermal melanocytes are supposed to be clinically affected by NF1 gene defects. The NF1 gene shares sequence homology with the p120 GTPase activating protein (p120-GAP) and neurofibromin has been shown to participate in Ras-regulation. By immunoprecipitation and Western blotting, neurofibromin was found to be expressed in melanocytes from the unaffected skin and café au lait macules of NF1 patients, but the intensity of the neurofibromin band was decreased compared to control cultures. The Ras-GTP/Ras-GDP ratios of NF1 derived melanocyte cultures were comparable to those derived from healthy donors. Furthermore, the total GAP-activity of cell lysates was not altered in NF1 melanocyte cultures compared to controls. However, lysates of proliferating melanocytes, both from NF1 patients and from healthy donors, showed an about 2-fold higher GAP-activity than poorly growing cells. Neurofibromin contributed approximately one third of total GAP-activity, in both control and NF1 melanocytes, indicating that it is not the major regulator of Ras in these cells. These results suggest that the function of neurofibromin in melanocytes is not limited to regulation of Ras activity.
登录
查看更多内容
神经纤维蛋白在发育中的大鼠和人类皮肤中定位于角质形成细胞和黑素细胞。
DOI：
10.1111/1523-1747.ep12379925
发表时间：
1994
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Malhotra,R;Ratner,N
通讯作者：
Ratner,N
影响因子：
3.5
作者：
BERNARDS, A;SNIJDERS, AJ;GUSELLA, JF
通讯作者：
GUSELLA, JF
影响因子：
6.5
作者：
HALABAN, R;GHOSH, S;LERNER, AB
通讯作者：
LERNER, AB
DOI：
10.1073/pnas.88.21.9658
发表时间：
1991-11-01
影响因子：
11.1
作者：
GUTMANN, DH;WOOD, DL;COLLINS, FS
通讯作者：
COLLINS, FS