PDGF regulates the actin cytoskeleton through hnRNP-K-mediated activation of the ubiquitin E3-ligase MIR.

The EMBO Journal
Kohji NaganoSoren Naaby-Hansen

Abstract

PDGF is a potent chemotactic mitogen and a strong inductor of fibroblast motility. In Swiss 3T3 fibroblasts, exposure to PDGF but not EGF or IGF-1 causes a rapid loss of actin stress fibers (SFs) and focal adhesions (FAs), which is followed by the development of retractile dendritic protrusions and induction of motility. The PDGF-specific actin reorganization was blocked by inhibition of Src-kinase and the 26S proteasome. PDGF induced Src-dependent association between the multifunctional transcription/translation regulator hnRNP-K and the mRNA-encoding myosin regulatory light-chain (MRLC)-interacting protein (MIR), a E(3)-ubiquitin ligase that is MRLC specific. This in turn rapidly increased MIR expression, and led to ubiquitination and proteasome-mediated degradation of MRLC. Downregulation of MIR by RNA muting prevented the reorganization of actin structures and severely reduced the migratory and wound-healing potential of PDGF-treated cells. The results show that activation of MIR and the resulting removal of diphosphorylated MRLC are essential for PDGF to instigate and maintain control over the actin-myosin-based contractile system in Swiss 3T3 fibroblasts. The PDGF induced protein destabilization through the regulation of ...Continue Reading

References

Feb 7, 1998·Science·A Hall
Oct 19, 2000·The Journal of Cell Biology·C JiménezA C Carrera
Jun 8, 2002·Molecular and Cellular Biology·Antje Ostareck-LedererMatthias W Hentze
Jun 27, 2003·The Journal of Biological Chemistry·Beat C BornhauserDan Lindholm
Jun 2, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Karol BomsztykJerzy Ostrowski
Sep 8, 2004·Journal of Molecular Biology·Karolina Klimek-TomczakJerzy Ostrowski
Nov 6, 2004·FEBS Letters·Agnieszka PaziewskaJerzy Ostrowski

❮ Previous
Next ❯

Citations

Jul 20, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ammad Ahmad FarooqiShahzad Bhatti
Jul 23, 2009·The Journal of Biological Chemistry·Marcel E MeimaDiane L Barber
Oct 24, 2008·The Journal of Biological Chemistry·Gaurav BajajJane E Ishmael
May 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Atsushi InoueRenu Wadhwa
Jul 15, 2015·Bioarchitecture·Sarah M Heissler, James R Sellers
Jan 28, 2012·The Biochemical Journal·Antje SchaeferPeter L Hordijk
Dec 7, 2017·International Journal of Molecular Sciences·Rupert DerlerAndreas Kungl
Aug 19, 2009·Cellular and Molecular Life Sciences : CMLS·Dan LindholmLaura Korhonen
Sep 12, 2020·Molecular Neurobiology·Büşra ŞengülDuygu Gezen-Ak

❮ Previous
Next ❯

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.