The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor.
The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor.
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膜蛋白CD9/DARAP 27增强了膜锚定的肝素结合EGF类似EGF的生长因子的近距离生长因子活性。
DOI：
10.1083/jcb.128.5.929
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发表时间：
1995-03
影响因子：
7.8
通讯作者：
MEKADA, E
中科院分区：
文献类型：
--
作者：
HIGASHIYAMA, S;IWAMOTO, R;GOISHI, K;RAAB, G;TANIGUCHI, N;KLAGSBRUN, M;MEKADA, E
膜锚定的肝素结合EGF样生长因子前体（proHB-EGF）/白喉毒素受体（DTR）属于一类跨膜生长因子，并且与也是跨膜蛋白的CD 9/DRAP 27物理缔合。为了评价proHB-EGF/DTR作为促细胞生长因子的生物学活性及其与CD 9/DRAP 27结合的生物学意义，使用表达人proHB-EGF/DTR和猴CD 9/DRAP 27两者或单独一种的小鼠L细胞的稳定转染子分析proHB-EGF/DTR的促有丝分裂活性。通过测量共培养物中的细胞刺激EGF受体配体依赖性细胞系EP 170.7中的DNA合成的能力来测定邻他克林活性。表达人proHB-EGF/DTR的LH-2细胞适度刺激EP170.7细胞生长。然而，LCH-1细胞，一种同时表达人proHB-EGF/DTR和猴CD 9/DRAP 27 cDNA的稳定共转染子，显著地不调节proHB-EGF/DTR的促肾上腺皮质激素生长因子活性，约为LH-2细胞的25倍，即使两种细胞类型在细胞表面表达相似水平的proHB-EGF/DTR。不能中和可溶性HB-EGF的促有丝分裂活性的抗-CD 9/DRAP 27抗体抑制LCH-1细胞胞内分泌生长活性的程度与抗-HB-EGF中和抗体和CRM 197（人HG-EGF的特异性抑制剂）相同。这些发现表明，proHB-EGF/DTR的阿曲他克林生长活性的最佳表达需要CD 9/DRAP 27的共表达。这些研究还表明，以前在可溶性生长因子中观察到的生长因子增强作用也发生在细胞表面相关生长因子水平。
The membrane-anchored heparin-binding EGF-like growth factor precursor (proHB-EGF)/diphtheria toxin receptor (DTR) belongs to a class of transmembrane growth factors and physically associates with CD9/DRAP27 which is also a transmembrane protein. To evaluate the biological activities of proHB-EGF/DTR as a juxtacrine growth factor and the biological significance of its association with CD9/DRAP27, the mitogenic activity of proHB-EGF/DTR was analyzed using stable transfectants of mouse L cells expressing both human proHB-EGF/DTR and monkey CD9/DRAP27, or either one alone. Juxtacrine activity was assayed by measuring the ability of cells in co-culture to stimulate DNA synthesis in an EGF receptor ligand dependent cell line, EP170.7. LH-2 cells expressing human proHB-EGF/DTR stimulated EP170.7 cell growth moderately. However, LCH-1 cells, a stable co-transfectant expressing both human proHB-EGF/DTR and monkey CD9/DRAP27 cDNAs, dramatically unregulated the juxtacrine growth factor activity of proHB-EGF/DTR approximately 25 times over that of LH-2 cells even though both cell types expressed similar levels of proHB-EGF/DTR on the cell surface. Anti-CD9/DRAP27 antibodies which were not able to neutralize the mitogenic activity of soluble HB-EGF suppressed LCH-1 cell juxtacrine growth activity to the same extent as did anti-HB-EGF neutralizing antibodies and CRM 197, specific inhibitors of human HG-EGF. These findings suggest that optimal expression of the juxtacrine growth activity of proHB-EGF/DTR requires co-expression of CD9/DRAP27. These studies also indicate that growth factor potentiation effects which have been observed previously for soluble growth factors also occurs at the level of cell surface associated growth factors.
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DOI：
10.1073/pnas.88.11.4671
发表时间：
1991-06-01
影响因子：
11.1
作者：
BRANNAN, CI;LYMAN, SD;COPELAND, NG
通讯作者：
COPELAND, NG
DOI：
10.1091/mbc.1.11.811
发表时间：
1990-10-01
期刊：
CELL REGULATION
影响因子：
--
作者：
BESNER, G;HIGASHIYAMA, S;KLAGSBRUN, M
通讯作者：
KLAGSBRUN, M
DOI：
10.1073/pnas.90.9.3889
发表时间：
1993-05-01
影响因子：
11.1
作者：
MARIKOVSKY, M;BREUING, K;KLAGSBRUN, M
通讯作者：
KLAGSBRUN, M
影响因子：
64.5
作者：
DERYNCK, R;ROBERTS, AB;GOEDDEL, DV
通讯作者：
GOEDDEL, DV
影响因子：
2.9
作者：
FEN, Z;DHADLY, MS;LEE, ME
通讯作者：
LEE, ME