Diaz Francisco Mendez, -Godinez David Sanchez, Solano Francisco, Jasani Akshi, Alcaide-Gavilan Maria, Prichard Beth E, Kellogg Douglas R
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, 95064.
Mol Biol Cell. 2025 Aug 1;36(8):ar94. doi: 10.1091/mbc.E24-12-0568. Epub 2025 Jun 4.
Cell-cycle progression is dependent upon cell growth. Cells must therefore translate growth into a proportional signal that indicates when there has been sufficient growth for cell-cycle progression. In budding yeast, the protein kinase Gin4 is required for normal control of bud growth and undergoes gradual multisite hyperphosphorylation and activation that are dependent upon bud growth and correlated with the extent of growth. Together, these observations suggest that Gin4 functions in mechanisms that measure cell growth. Here, we searched for signals that link Gin4 hyperphosphorylation to cell growth. We found that Elm1, a yeast homologue of mammalian Lkb1 kinases, is sufficient in vitro to induce full hyperphosphorylation of Gin4, and likely works by stimulating extensive autophosphorylation of Gin4. We further discovered that casein kinase Iγ, encoded by the and genes, is required for growth-dependent phosphorylation of Gin4. Yck1/2 are delivered to the growing plasma membrane by post-Golgi vesicles that drive membrane growth, and they are required for normal control of growth. The data suggest that delivery of Yck1/2 to the plasma membrane could play an important role in generating a growth-dependent signal that provides a measure of bud growth.
细胞周期进程依赖于细胞生长。因此，细胞必须将生长转化为一个成比例的信号，以指示何时已实现足以推动细胞周期进程的生长。在芽殖酵母中，蛋白激酶Gin4是芽生长正常调控所必需的，它会经历逐渐的多位点过度磷酸化和激活，这依赖于芽的生长且与生长程度相关。这些观察结果共同表明，Gin4在衡量细胞生长的机制中发挥作用。在此，我们寻找将Gin4过度磷酸化与细胞生长联系起来的信号。我们发现，哺乳动物Lkb1激酶的酵母同源物Elm1在体外足以诱导Gin4的完全过度磷酸化，并且可能通过刺激Gin4的广泛自磷酸化起作用。我们进一步发现，由 和 基因编码的酪蛋白激酶Iγ是Gin4生长依赖性磷酸化所必需的。Yck1/2通过驱动膜生长的高尔基体后囊泡被递送至生长中的质膜，它们是生长正常调控所必需的。数据表明，Yck1/2向质膜的递送可能在产生一个提供芽生长度量的生长依赖性信号中发挥重要作用。
