Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation

Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation
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DOI:
10.1038/sj.onc.1201039
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发表时间:
1997-05-01
期刊:
影响因子:
8
通讯作者:
Godowski, PJ
Godowski, PJ
中科院分区:
医学1区
文献类型:
--
作者:
Chen, J;Carey, K;Godowski, PJ

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Mer/尼克/Eyk是一种孤儿受体酪氨酸激酶,在单核细胞和来源于上皮和生殖组织的细胞中高水平表达。Mer的过表达与淋巴恶性肿瘤有关。在这里,我们确定Gas 6,生长停滞特异性基因的产物,作为Mer的配体。Gas 6先前已显示激活Axl和Rse/Tyro 3两者,这两种其他受体酪氨酸激酶与Mer在同一家族中。使用表面等离子体共振比较了Gas 6与可溶性Axl、Rse/Tyro 3和Mer的表观相对缔合和解离速率常数。Gas 6显示诱导在几种不同类型的细胞中表达的Mer的快速磷酸化。我们还观察到一个短暂的激活p42 MAP激酶激活Mer的Gas 6。因此,Gas 6通过多种受体酪氨酸激酶发挥其生物学作用。
Mer/Nyk/Eyk is an orphan receptor tyrosine kinase expressed at high levels in monocytes and cells derived from epithelial and reproductive tissues. Overexpression of Mer has been associated with lymphoid malignancies. Here we identify Gas6, the product of a growth arrest specific gene, as a ligand for Mer. Gas6 has previously been shown to activate both Axl and Rse/Tyro3, two other receptor tyrosine kinases in the same family as Mer. The apparent relative association and dissociation rate constants of Gas6 for soluble Axl, Rse/Tyro3 and Mer were compared using surface plasmon resonance. Gas6 was shown to induce rapid phosphorylation of Mer expressed in several different types of cells. We also observed a transient activation of p42 MAP kinase following activation of Mer by Gas6. Thus, Gas6 exerts its biological effects through multiple receptor tyrosine kinases.