LATS2 Q9NRM7

丝氨酸/苏氨酸蛋白激酶LATS2 (EC 2.7.11.1) (有丝分裂期间磷酸化激酶蛋白) (大肿瘤抑制因子同源物2) (丝氨酸/苏氨酸蛋白激酶kpm) (Warts样激酶)

功能描述

Hippo信号通路中YAP1的负调控因子，通过限制增殖和促进凋亡，在器官大小控制和肿瘤抑制中发挥关键作用 (PubMed:18158288, PubMed:26437443, PubMed:26598551, PubMed:34404733)。该通路的核心由激酶级联反应组成，其中STK3/MST2和STK4/MST1与其调节蛋白SAV1形成复合物，磷酸化并激活与调节蛋白MOB1形成复合物的LATS1/2，进而磷酸化并灭活YAP1癌蛋白和WWTR1/TAZ (PubMed:26437443, PubMed:26598551, PubMed:34404733)。LATS2对YAP1的磷酸化抑制其易位至细胞核，从而调节对细胞增殖、细胞死亡和细胞迁移至关重要的细胞基因 (PubMed:26598551, PubMed:34404733)。响应细胞接触抑制驱动的WWP1对AMOTL2的泛素化，也磷酸化YAP1，导致LATS2激活 (PubMed:34404733)。作为肿瘤抑制因子，在中心体复制、维持有丝分裂保真度和基因组稳定性方面发挥关键作用 (PubMed:10871863)。通过下调cyclin E/CDK2激酶活性负调控G1/S期转换 (PubMed:12853976)。雄激素受体的负调控因子 (PubMed:15131260)。磷酸化细胞核内的SNAI1导致其核滞留和稳定，从而增强其上皮-间质转化和肿瘤细胞侵袭/迁移活性 (PubMed:21952048)。这种肿瘤促进作用独立于其对YAP1或WWTR1/TAZ的影响 (PubMed:21952048)。作为NLRP3炎症小体的激活因子，通过介导NLRP3棕榈酰化后其Ser-265位点的磷酸化，促进NEK7对NLRP3的激活 (PubMed:39173637)。 {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976, ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:39173637}。

组织特异性

Expressed at high levels in heart and skeletal muscle and at lower levels in all other tissues examined.

亚细胞定位

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm. Cytoplasm, cytoskeleton, spindle pole. Nucleus. Note=Colocalizes with AURKA at the centrosomes during interphase, early prophase and cytokinesis. Migrates to the spindle poles during mitosis, and to the midbody during cytokinesis. Translocates to the nucleus upon mitotic stress by nocodazole treatment.