Dok-1 independently attenuates Ras/mitogen-activated protein kinase and Src/c-myc pathways to inhibit platelet-derived growth factor-induced mitogenesis

Molecular and Cellular Biology
Mingming ZhaoLinda Van Aelst

Abstract

The Dok adaptor proteins play key regulatory roles in receptor and non-receptor kinase-initiated signaling pathways. Dok-1, the prototype member of this family, negatively regulates cell proliferation elicited by numerous growth factors, including platelet-derived growth factor (PDGF). However, how Dok-1 exerts its negative effect on mitogenesis has remained elusive. Using Dok-1 knockout cells and Dok-1 mutants deficient in binding to specific Dok-1-interacting proteins, we show that Dok-1 interferes with PDGF-stimulated c-myc induction and Ras/mitogen-activated protein kinase (MAPK) activation by tethering different signaling components to the cell membrane. Specifically, Dok-1 attenuates PDGF-elicited c-myc induction by recruiting Csk to active Src kinases, whereupon their activities and consequent c-myc induction are diminished. On the other hand, Dok-1 negatively regulates PDGF-induced MAPK activation by acting on Ras-GAP and at least one other Dok-1-interacting protein. Importantly, we demonstrate that Dok-1's actions on both of these signaling pathways contribute to its inhibitory effect on mitogenesis. Our data suggest a mechanistic basis for the inhibitory effect of Dok-1 on growth factor-induced mitogenesis and its rol...Continue Reading

References

Sep 18, 1992·Cell·C L SawyersO N Witte
Feb 1, 1994·The Journal of Clinical Investigation·C A CartwrightB M Egbert
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Y YamanashiT Yamamoto
Jun 18, 1993·Cell·J A Cooper, B Howell
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
Jan 22, 1998·Current Opinion in Structural Biology·F Sicheri, J Kuriyan
Mar 28, 1998·The Journal of Biological Chemistry·A Di CristofanoM D Resh
Aug 8, 1998·Trends in Cell Biology·C BouchardM Eilers
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·N KashigeR Kobayashi
Mar 25, 2000·Molecular and Cellular Biology·S LemayA Veillette
Oct 24, 2000·The Journal of Biological Chemistry·Z SongyangD Baltimore
Nov 14, 2000·Molecular and Cellular Biology·R A BlakeS A Courtneidge
Feb 15, 2001·Nature Cell Biology·S M Jones, A Kazlauskas
Feb 27, 2001·FEBS Letters·M FioriniO Segatto
Apr 18, 2001·Methods in Enzymology·B BoettnerL Van Aelst
Jun 5, 2001·Nature Cell Biology·M ChiarielloJ S Gutkind
Jun 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·T BowmanR Jove
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
May 4, 2002·Nature Cell Biology·Vi K ChiuMark R Philips
May 22, 2002·Biochimica Et Biophysica Acta·Margaret C Frame
Oct 29, 2003·Current Opinion in Chemical Biology·Philip A ColeDongxia Wang

❮ Previous
Next ❯

Citations

Jun 7, 2007·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Bishwanath ChatterjeeCecilia Lo
Feb 9, 2010·Nature Genetics·Alice H BergerPier Paolo Pandolfi
Aug 30, 2008·Nature Reviews. Immunology·Oreste AcutoFrédérique Michel
Jul 23, 2011·Genes & Cancer·Thomas GrewalCarlos Enrich
Dec 2, 2011·Annals of Surgical Oncology·Hiromichi MiyagakiYuichiro Doki
Nov 21, 2013·PloS One·Alice H BergerPier Paolo Pandolfi
Nov 12, 2013·Oncogene·M Hrdinka, V Horejsi
Sep 16, 2011·Science Signaling·Jamie R SchoenbornArthur Weiss
Aug 13, 2008·The Journal of Cell Biology·Laurence VeraciniChristine Benistant
Mar 15, 2011·Biochimica Et Biophysica Acta·Lee HeddenStephen P Soltoff
Nov 17, 2009·Immunological Reviews·Ryuichi MashimaYuji Yamanashi
Jul 29, 2011·International Journal of Cancer. Journal International Du Cancer·Amandine SaulnierBakary S Sylla
Dec 5, 2012·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ryuichi MashimaYuji Yamanashi
Aug 23, 2011·Molecular Oncology·Pierre-Luc MercierDimcho Bachvarov
May 3, 2008·PLoS Pathogens·Natalia SharovaMario Stevenson
Jul 20, 2016·EBioMedicine·Igor Astsaturov
Jan 5, 2014·The Journal of Biological Chemistry·Sascha C HughanShaun P Jackson
Jan 11, 2020·Molecular Biology Reports·Esin TunaNur Buyru
Mar 18, 2015·Biological Chemistry·Anne HennigIgnacio Rubio
Feb 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica G BorgerRose Zamoyska
May 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Gaëtan BlaizeRenaud Lesourne

❮ 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.