Goruppi S, Ruaro E, Schneider C
L.N.C.I.B. (Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, Trieste, Italy.
Oncogene. 1996 Feb 1;12(3):471-80.
Reversible growth arrest has been characterised for enhanced expression of a set of genes called gas (growth arrest specific). gas6 product (Gas6) is a secreted protein that was identified as the ligand for the tyrosine kinase receptor Axl. Here we report that Gas6 is able to induce cell cycle division entry in serum starved NIH3T3 cells. This mitogenic activity of Gas6 strictly correlates with its ability to interact with NIH3T3 endogenous Axl receptor since it can be abolished by soluble Axl extracellular domain and activates both Axl intrinsic kinase activity and the downstream MAPK pathway. Moreover when ectopic Axl overexpression is performed by microinjection in serum starved NIH3T3 cells, addition of a non mitogenic level of Gas6 induces selective entry into S phase in Axl overexpressing cells. Interestingly, Axl overexpression per se is not able to induce S phase entry. Finally we present evidences indicating that Gas6 is able to protect serum starved NIH3T3 cells from cell death by apoptosis as induced by complete growth factor depletion. The reported survival activity seems to be independent of Gas6 mitogenic activity, thus implicating a double and separable activity for Gas6 during growth arrest.
可逆性生长停滞的特征在于一组称为gas（生长停滞特异性）的基因表达增强。gas6产物（Gas6）是一种分泌蛋白，被鉴定为酪氨酸激酶受体Axl的配体。在此我们报告，Gas6能够诱导血清饥饿的NIH3T3细胞进入细胞周期分裂。Gas6的这种促有丝分裂活性与其与NIH3T3内源性Axl受体相互作用的能力密切相关，因为它可被可溶性Axl细胞外结构域消除，并激活Axl内在激酶活性和下游MAPK途径。此外，当通过显微注射在血清饥饿的NIH3T3细胞中进行异位Axl过表达时，添加非促有丝分裂水平的Gas6会诱导Axl过表达细胞选择性进入S期。有趣的是，Axl过表达本身并不能诱导进入S期。最后，我们提供的证据表明，Gas6能够保护血清饥饿的NIH3T3细胞免于因完全生长因子耗尽诱导的凋亡而导致的细胞死亡。所报道的生存活性似乎独立于Gas6的促有丝分裂活性，因此暗示Gas6在生长停滞期间具有双重且可分离的活性。
