ONCOSTATIN-M STIMULATES TYROSINE PROTEIN-PHOSPHORYLATION IN PARALLEL WITH THE ACTIVATION OF P42(MAPK)/ERK-2 IN KAPOSI CELLS - EVIDENCE THAT THIS PATHWAY IS IMPORTANT IN KAPOSI CELL-GROWTH
ONCOSTATIN-M STIMULATES TYROSINE PROTEIN-PHOSPHORYLATION IN PARALLEL WITH THE ACTIVATION OF P42(MAPK)/ERK-2 IN KAPOSI CELLS - EVIDENCE THAT THIS PATHWAY IS IMPORTANT IN KAPOSI CELL-GROWTH
复制标题
DOI：
10.1172/jci116659
复制
发表时间：
1993-08-01
影响因子：
15.9
通讯作者：
NEL, AE
中科院分区：
文献类型：
--
作者：
AMARAL, MC;MILES, S;NEL, AE
肿瘤抑制素- m （OSM）是卡波西氏肉瘤（KS）细胞的一种有效的丝裂原。我们在三个艾滋病相关的KS系中研究了OSM受体的信号传导，并显示了145-、120-、85-和42-kD底物的酪氨酸磷酸化诱导。42-kD底物被鉴定为p42MAPK（丝裂原活化蛋白激酶），也称为ERK-2。这种丝氨酸/苏氨酸激酶将来自受体酪氨酸蛋白激酶（TPKs）或受体相关TPKs的有丝分裂信号传递给转录激活因子。OSM对MAP激酶激活和诱导KS细胞生长的剂量依赖性几乎相同，提示功能联系。MAP激酶的激活依赖于酪氨酸磷酸化，osm诱导的MAP激酶活性和KS细胞生长均可被TPK抑制剂、染料木素和格尔达霉素抑制。OSM还刺激了人静脉内皮细胞中类似底物的酪氨酸磷酸化和MAP激酶活性。虽然已经提出OSM受体可能包括IL-6受体的gp130亚基和白血病抑制因子（LIF）受体的α链，但在KS细胞中，LIF和r - IL-6都不能诱导酪氨酸蛋白磷酸化或p42MAPK激活。然而，在人B细胞系AF-10中，r - il -6确实刺激酪氨酸磷酸化和p42MAPK活性，而OSM和LIF没有影响。我们的研究结果表明，尽管OSM和IL-6受体共享一个共同的信号通路，但该通路在卡波西氏细胞中被OSM选择性激活。
Oncostatin-M (OSM) is a potent mitogen for Kaposi's sarcoma (KS) cells. We studied signaling by the OSM receptor in three AIDS-related KS lines and show induction of tyrosine phosphorylation of 145-, 120-, 85-, and 42-kD substrates. The 42-kD substrate was identified as p42MAPK (mitogen-activated protein kinase), also known as ERK-2. This serine/threonine kinase relays mitogenic signals from receptor tyrosine protein kinases (TPKs) or receptor-associated TPKs to transcriptional activators. The OSM dose dependence for MAP kinase activation and induction of KS cell growth were almost identical, suggesting functional linkage. MAP kinase activation was dependent on tyrosine phosphorylation, and both OSM-induced MAP kinase activity and KS cell growth could be suppressed by TPK inhibitors, genistein and geldanomycin. OSM also stimulated tyrosine phosphorylation of similar substrates and MAP kinase activity in human vein endothelial cells. While it has been proposed that the OSM receptor may include the gp130 subunit of the IL-6 receptor and alpha-chain of leukemia inhibitory factor (LIF) receptor, neither LIF nor r.IL-6 induced tyrosine protein phosphorylation or p42MAPK activation in KS cells. However, r.IL-6 did stimulate tyrosine phosphorylation and p42MAPK activity in the human B cell line, AF-10, while OSM and LIF exerted no effects. Our results indicate that, although the OSM and IL-6 receptors share a common signaling pathway, this pathway is selectively activated by OSM in Kaposi's cells.