scholarly journals Regulation of Smoothened Phosphorylation and High-Level Hedgehog Signaling Activity by a Plasma Membrane Associated Kinase

PLoS Biology ◽  
2016 ◽  
Vol 14 (6) ◽  
pp. e1002481 ◽  
Author(s):  
Shuangxi Li ◽  
Shuang Li ◽  
Yuhong Han ◽  
Chao Tong ◽  
Bing Wang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Hedgehog Signaling ◽  
High Level ◽  
Signaling Activity

scholarly journals Competition between two phosphatases fine-tunes Hedgehog signaling

2020 ◽  
Vol 220 (2) ◽  
Author(s):  
Min Liu ◽  
Aiguo Liu ◽  
Jie Wang ◽  
Yansong Zhang ◽  
Yajuan Li ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Phosphatase Activity ◽  
Protein Phosphatase ◽  
Hedgehog Signaling ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Feedback Mechanisms ◽  
Hh Signaling ◽  
High Level ◽  
Signaling Activity

Hedgehog (Hh) signaling is essential for embryonic development and adult homeostasis. How its signaling activity is fine-tuned in response to fluctuated Hh gradient is less known. Here, we identify protein phosphatase V (PpV), the catalytic subunit of protein phosphatase 6, as a homeostatic regulator of Hh signaling. PpV is genetically upstream of widerborst (wdb), which encodes a regulatory subunit of PP2A that modulates high-level Hh signaling. We show that PpV negatively regulates Wdb stability independent of phosphatase activity of PpV, by competing with the catalytic subunit of PP2A for Wdb association, leading to Wdb ubiquitination and subsequent proteasomal degradation. Thus, regulated Wdb stability, maintained through competition between two closely related phosphatases, ensures graded Hh signaling. Interestingly, PpV expression is regulated by Hh signaling. Therefore, PpV functions as a Hh activity sensor that regulates Wdb-mediated PP2A activity through feedback mechanisms to maintain Hh signaling homeostasis.

scholarly journals High level expression of transfected G protein αi3subunit is required for plasma membrane targeting and adenylyl cyclase inhibition in NIH 3T3 fibroblasts

FEBS Letters ◽  
1992 ◽  
Vol 312 (2-3) ◽  
pp. 223-228 ◽  
Author(s):  
Sylvie Hermouet ◽  
Philippe de Mazancourt ◽  
Allen M. Spiegel ◽  
Marilyn Gist Farquhar ◽  
Bridget S. Wilson
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Membrane Targeting ◽  
High Level Expression ◽  
3T3 Fibroblasts ◽  
High Level ◽  
Nih 3T3

scholarly journals An ABC transporter Wzm–Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria

2021 ◽  
Vol 118 (17) ◽  
pp. e2023663118
Author(s):  
Karin Savková ◽  
Stanislav Huszár ◽  
Peter Baráth ◽  
Zuzana Pakanová ◽  
Stanislav Kozmon ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Abc Transporter ◽  
Morphological Changes ◽  
Transport Systems ◽  
Host Immune System ◽  
Mycolic Acids ◽  
Cell Wall Biogenesis ◽  
Covalently Linked ◽  
High Level

Mycobacterium tuberculosis, one of the deadliest pathogens in human history, is distinguished by a unique, multilayered cell wall, which offers the bacterium a high level of protection from the attacks of the host immune system. The primary structure of the cell wall core, composed of covalently linked peptidoglycan, branched heteropolysaccharide arabinogalactan, and mycolic acids, is well known, and numerous enzymes involved in the biosynthesis of its components are characterized. The cell wall biogenesis takes place at both cytoplasmic and periplasmic faces of the plasma membrane, and only recently some of the specific transport systems translocating the metabolic intermediates between these two compartments have been characterized [M. Jackson, C. M. Stevens, L. Zhang, H. I. Zgurskaya, M. Niederweis, Chem. Rev., 10.1021/acs.chemrev.0c00869 (2020)]. In this work, we use CRISPR interference methodology in Mycobacterium smegmatis to functionally characterize an ATP-binding cassette (ABC) transporter involved in the translocation of galactan precursors across the plasma membrane. We show that genetic knockdown of the transmembrane subunit of the transporter results in severe morphological changes and the accumulation of an aberrantly long galactan precursor. Based on similarities with structures and functions of specific O-antigen ABC transporters of gram-negative bacteria [C. Whitfield, D. M. Williams, S. D. Kelly, J. Biol. Chem. 295, 10593-10609 (2020)], we propose a model for coupled synthesis and export of the galactan polymer precursor in mycobacteria.

scholarly journals Rab23, a Negative Regulator of Hedgehog Signaling, Localizes to the Plasma Membrane and the Endocytic Pathway

Traffic ◽  
2003 ◽  
Vol 4 (12) ◽  
pp. 869-884 ◽  
Author(s):  
Timothy M. Evans ◽  
Charles Ferguson ◽  
Brandon J. Wainwright ◽  
Robert G. Parton ◽  
Carol Wicking
Keyword(s):  
Plasma Membrane ◽  
Hedgehog Signaling ◽  
Endocytic Pathway ◽  
Negative Regulator

Gant61 ameliorates CCl4-induced liver fibrosis by inhibition of Hedgehog signaling activity

2020 ◽  
Vol 387 ◽  
pp. 114853 ◽  
Author(s):  
Shen Jiayuan ◽  
Yan Junyan ◽  
Wei Xiangzhen ◽  
Liu Zuping ◽  
Ni Jian ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hedgehog Signaling ◽  
Signaling Activity

The E6/E7 oncogenes of human papilloma virus and estradiol regulate hedgehog signaling activity in a murine model of cervical cancer

2019 ◽  
Vol 381 (2) ◽  
pp. 311-322 ◽  
Author(s):  
Verónica Rojo-León ◽  
Celina García ◽  
Concepción Valencia ◽  
Marco-Antonio Méndez ◽  
Christopher Wood ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Murine Model ◽  
Hedgehog Signaling ◽  
Papilloma Virus ◽  
Signaling Activity
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