Chen J, Carey K, Godowski P J
Department of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA.
Oncogene. 1997 May 1;14(17):2033-9. doi: 10.1038/sj.onc.1201039.
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.
Mer/Nyk/Eyk是一种孤儿受体酪氨酸激酶，在单核细胞以及源自上皮组织和生殖组织的细胞中高表达。Mer的过表达与淋巴恶性肿瘤有关。在此我们鉴定出一种生长停滞特异性基因的产物Gas6为Mer的配体。Gas6此前已被证明可激活Axl以及Rse/Tyro3，这是与Mer同一家族的另外两种受体酪氨酸激酶。使用表面等离子体共振比较了Gas6与可溶性Axl、Rse/Tyro3和Mer的表观相对结合和解离速率常数。结果表明Gas6可诱导在几种不同类型细胞中表达的Mer快速磷酸化。我们还观察到Gas6激活Mer后p42丝裂原活化蛋白激酶出现短暂激活。因此，Gas6通过多种受体酪氨酸激酶发挥其生物学效应。
