跳转至内容
Merck
CN
  • Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.

Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.

Cell (2020-08-28)
Jason Z Zhang, Tsan-Wen Lu, Lucas M Stolerman, Brian Tenner, Jessica R Yang, Jin-Fan Zhang, Martin Falcke, Padmini Rangamani, Susan S Taylor, Sohum Mehta, Jin Zhang
摘要

The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.

材料
货号
品牌
产品描述

Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
2-巯基乙醇, ≥99.0%
Sigma-Aldrich
3-异丁基-1-甲基黄嘌呤, ≥99% (HPLC), powder
Sigma-Aldrich
聚-D-赖氨酸 氢溴酸盐, mol wt 70,000-150,000, lyophilized powder, γ-irradiated, BioReagent, suitable for cell culture
Sigma-Aldrich
ITS液体培养基补充剂(100x), liquid, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
MES, low moisture content, ≥99% (titration)
Sigma-Aldrich
3-异丁基-1-甲基黄嘌呤, ≥99%, BioUltra
Sigma-Aldrich
乙二醇-双(2-氨基乙醚)-N,N,N′,N′-四乙酸, for molecular biology, ≥97.0%
Sigma-Aldrich
DL-二硫苏糖醇, ≥98% (HPLC), ≥99.0% (titration)
Sigma-Aldrich
IPTG, ≥99% (TLC), ≤0.1% Dioxane
Sigma-Aldrich
腺苷 5'-三磷酸 二钠盐 水合物, 99%
Sigma-Aldrich
1,6-己二醇, 99%
Sigma-Aldrich
乙二胺四乙酸, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
腺苷-3′,5′-环单磷酸, ≥98.5% (HPLC), powder
Sigma-Aldrich
1-丁基-3-甲基咪唑六氟磷酸盐, ≥97.0% (HPLC)
USP
异丙肾上腺素 盐酸盐, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
鸟苷 3',5'-环单磷酸, ≥98% (HPLC), powder
Sigma-Aldrich
咯利普兰, solid, ≥98% (HPLC)
Sigma-Aldrich
MDL-12,330A 盐酸盐, ≥98% (HPLC), powder