The lysosome is a cellular signalling hub at the point of convergence of endocytic and autophagic pathways, where the contents are degraded and recycled. Pleckstrin homology domain-containing family member 1 (PLEKHM1) acts as an adaptor to facilitate the fusion of endocytic and autophagic vesicles with the lysosome. However, it is unclear how PLEKHM1 function at the lysosome is controlled. Herein, we show that PLEKHM1 co-precipitates with, and is directly phosphorylated by, mTOR. Using a phospho-specific antibody against Ser432/S435 of PLEKHM1, we show that the same motif is a direct target for ERK2-mediated phosphorylation in a growth factor-dependent manner. This dual regulation of PLEKHM1 at a highly conserved region points to a convergence of both growth factor- and amino acid-sensing pathways, placing PLEKHM1 at a critical juncture of cellular metabolism.

中文翻译：

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内溶酶体接头 PLEKHM1 是 mTOR 和 MAPK 通路的直接目标

溶酶体是内吞和自噬途径汇合点的细胞信号中枢，其中的内容物被降解和回收。含有 Pleckstrin 同源结构域的家族成员 1 (PLEKHM1) 充当适配器以促进内吞和自噬囊泡与溶酶体的融合。然而，目前尚不清楚 PLEKHM1 在溶酶体中的功能是如何控制的。在此，我们表明 PLEKHM1 与 mTOR 共沉淀并被 mTOR 直接磷酸化。使用针对 PLEKHM1 的 Ser432/S435 的磷酸化特异性抗体，我们表明相同的基序是以生长因子依赖的方式是 ERK2 介导的磷酸化的直接目标。PLEKHM1 在高度保守区域的这种双重调节表明生长因子和氨基酸传感途径的收敛，