Signaling crosstalk between TGFβ and Dishevelled/Par1b.

Cell Death and Differentiation
Anant MamidiStefano Piccolo

Abstract

Crosstalk of signaling pathways is critical during metazoan development and adult tissue homeostasis. Even though the transforming growth factor-beta (TGFβ) transduction cascade is rather simple, in vivo responsiveness to TGFβ ligands is tightly regulated at several steps. As such, TGFβ represents a paradigm for how the activity of one signaling system is modulated by others. Here, we report an unsuspected regulatory step involving Dishevelled (Dvl) and Par1b (also known as MARK2). Dvl and Par1b cooperate to enable TGFβ/bone morphogenetic protein (BMP) signaling in Xenopus mesoderm development and TGFβ responsiveness in mammalian cells. Mechanistically, the assembly of the Par1b/Dvl3/Smad4 complex is fostered by Wnt5a. The association of Smad4 to Dvl/Par1 prevents its inhibitory ubiquitination by ectodermin (also known as transcriptional intermediary factor 1 gamma or tripartite motif protein 33). We propose that this crosstalk is relevant to coordinate TGFβ responses with Wnt-noncanonical and polarity pathways.

References

May 16, 2000·Nature·J B WallingfordR M Harland
Mar 17, 2001·Nature Reviews. Genetics·E M De RobertisO Wessely
Feb 15, 2003·Developmental Cell·Michael OelgeschlägerE M De Robertis
May 22, 2004·Nature Reviews. Genetics·Christof Niehrs
Feb 22, 2005·Journal of Biology·Keiji ItohSergei Y Sokol
Jun 7, 2005·Current Biology : CB·Tae Joo ParkJohn B Wallingford
Feb 10, 2007·Molecular Cell·Gopal SapkotaJoan Massagué
Jun 27, 2007·Molecular and Cellular Biology·Laurence LevyCaroline S Hill
Nov 6, 2007·Developmental Cell·Bob Goldstein, Ian G Macara
Nov 26, 2008·Cell Research·Peter LönnAristidis Moustakas
Dec 17, 2008·Nature·Carlos Carmona-FontaineRoberto Mayor
Apr 7, 2009·Cell·Maddalena AdornoStefano Piccolo
Apr 15, 2009·Cell Research·Shih-Lei LaiRandall T Moon
Oct 27, 2009·Development·Aristidis Moustakas, Carl-Henrik Heldin
Nov 10, 2009·Cytokine & Growth Factor Reviews·Edward EiversE M De Robertis
Nov 18, 2009·Molecular Cell·Sheng GaoJoan Massagué
Oct 20, 2010·The Journal of Pathology·Erik Meulmeester, Peter Ten Dijke
May 21, 2011·EMBO Reports·Cédric HeslingRuth Rimokh

❮ Previous
Next ❯

Citations

Apr 25, 2015·International Journal of Cancer. Journal International Du Cancer·Roland HubauxWan L Lam
Jan 17, 2015·Trends in Cell Biology·Derek P BrazilFinian Martin
Nov 30, 2016·The Journal of Biological Chemistry·Adam D CosterSteven J Altschuler

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
antisense oligonucleotides
co-immunoprecipitation
co-IP
ubiquitination
deubiquitination
immunoprecipitation

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.