Src tyrosyl phosphorylates cortactin in response to prolactin.
Src tyrosyl phosphorylates cortactin in response to prolactin.
复制标题
Src 酪氨酰磷酸化皮质素以响应催乳素。
DOI：
10.1016/j.bbrc.2015.05.116
复制
发表时间：
2015
影响因子：
3.1
通讯作者：
Diakonova,Maria
中科院分区：
文献类型：
--
作者：
Hammer,Alan;Laghate,Sneha;Diakonova,Maria
激素/细胞因子催乳素（PRL）与乳腺癌细胞的侵袭和转移有关。prl诱导的途径由两种非受体酪氨酸激酶JAK2和Src介导。我们之前证明催乳素通过JAK2及其靶丝氨酸/苏氨酸激酶PAK1刺激乳腺癌细胞TMX2-28的侵袭。我们在此假设，肌动蛋白结合蛋白（actin-binding protein）是一种参与侵殖泡形成和细胞侵袭的蛋白，可被PRL激活。我们证明TMX2-28细胞对PRL的反应比T47D乳腺癌细胞更具侵袭性。我们发现，在TMX2-28细胞中，PRL对cortatin的酪氨酸磷酸化反应具有时间和剂量依赖性，而在T47D细胞中则没有。此外，我们发现PRL通过Src介导接触酪氨酸磷酸化，而不是通过JAK2介导。最后，我们证明prl介导的最大TMX2-28细胞入侵需要Src和JAK2激酶活性，而T47D细胞入侵依赖于JAK2而不依赖于Src。因此，PRL可能通过两种途径诱导细胞侵袭：通过我们之前证明的JAK2/PAK1介导的途径，以及src依赖性激活和酪氨酸磷酸化的接触蛋白。
The hormone/cytokine prolactin (PRL) is implicated in breast cancer cell invasion and metastasis. PRL-induced pathways are mediated by two non-receptor tyrosine kinases, JAK2 and Src. We previously demonstrated that prolactin stimulates invasion of breast cancer cells TMX2-28 through JAK2 and its target serine/threonine kinase PAK1. We hypothesize herein that the actin-binding protein cortactin, a protein involved in invadopodia formation and cell invasion, is activated by PRL. We demonstrate that TMX2-28 cells are more invasive than T47D breast cancer cells in response to PRL. We determine that cortactin is tyrosyl phosphorylated in response to PRL in a time and dose-dependent manner in TMX2-28 cells, but not in T47D cells. Furthermore, we show that PRL mediates cortactin tyrosyl phosphorylation via Src, but not JAK2. Finally, we demonstrate that maximal PRL-mediated TMX2-28 cell invasion requires both Src and JAK2 kinase activity, while T47D cell invasion is JAK2- but not Src-dependent. Thus PRL may induce cell invasion via two pathways: through a JAK2/PAK1 mediated pathway that we have previously demonstrated, and Src-dependent activation and tyrosyl phosphorylation of cortactin.