PPP1R2通过稳定动态子单元相互作用来刺激蛋白酸酶-1
Sarah Lemaire1, Mónica Ferreira1, Zander Claes1
1Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
Nature communications
|November 13, 2024
概括
蛋白酸酶1 (PP1) 功能是由调节子单元调节的. PPP1R2 (抑制剂-2) 稳定特定的PP1全酶,如PP1:RepoMan,促进基质脱化和细胞信号传递.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 蛋白质Ser/Thr酸酶PP1与调控子单元 (RIPPOs) 起作用.
- PPP1R2 (抑制剂-2) 是一种古老的RIPPO,在PP1活动中具有争论的作用.
- PPP1R2对细胞中的PP1的影响的确切机制尚不清楚.
研究的目的:
- 为了阐明PPP1R2如何影响蛋白质Ser/Thr phosphatasePP1在完整细胞中的功能.
- 研究PP1R2介导PP1全酶的PP1介导调节的基础分子机制.
主要方法:
- 利用特定的研究工具研究PP1:PPP1R2相互作用.
- 研究PP1R2对PP1全酶的招募的结构和功能后果.
- 分析了PPP1R2对PP1全酶稳定性和基质脱的影响.
主要成果:
- PPP1R2稳定了特定的PP1全酶,例如PP1:RepoMan.
- PPP1R2破坏了PP1内部的抑制相互作用,并创建了一个新的RepoMan结合部位.
- 稳定的PP1:RepoMan:PPP1R2复合体能够抵抗其他RIPPO的干扰.
结论:
- PPP1R2作为PP1全酶子集的稳定剂,增强其酸酶活性.
- PPP1R2通过改变全酶组成和稳定性来调节PP1的功能.
- 这种稳定机制提供了对PP1活动依赖的细胞信号通路调节的见解.
相关概念视频
Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
Phosphoinositides and PIPs
8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
Amplifying Signals via Enzymatic Cascade
8.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.3K
IP3/DAG Signaling Pathway
11.9K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.9K
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K


