Abstract：
Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on \"PAK1\", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.
摘要：
PAK1（RAC/CDC42激活激酶1）和TOR（雷帕霉素靶标）都是主要的致癌/老化激酶。然而,它们在我们的免疫系统中起着相反的作用，即免疫系统被PAK1抑制，而它需要TOR。因此，PAK1-阻断剂,对癌症的治疗更有效，比TOR-阻滞剂。自2015年以来，我们发现PDGF诱导的黑色素生成依赖于“PAK1”我们能够筛选出一系列PAK1阻断剂作为黑色素生成抑制剂,最终可以促进寿命.有趣的是,雷帕霉素,第一种TOR抑制剂，促进黑色素生成，清楚地表明TOR抑制黑色素生成。然而,一种名为TORin-1的新TOR抑制剂不再抑制免疫系统，并阻断细胞培养中的黑色素生成。这些观察强烈表明TORin-1作为PAK1受体阻滞剂，而不是TOR阻滞剂，在体内。因此，细胞培养中的黑素生成很可能使我们能够区分PAK1阻断剂和TORblockers.
