An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ.

Molecular and Cellular Biology
Z LuoJ Avruch

Abstract

The function of the c-Raf-1 zinc finger domain in the activation of the Raf kinase was examined by the creation of variant zinc finger structures. Mutation of Raf Cys 165 and Cys 168 to Ser strongly inhibits the Ras-dependent activation of c-Raf-1 by epidermal growth factor (EGF). Deletion of the Raf zinc finger and replacement with a homologous zinc finger from protein kinase C gamma (PKC gamma) (to give gamma/Raf) also abrogates EGF-induced activation but enables a vigorous phorbol myristate acetate (PMA)-induced activation. PMA activation of gamma/Raf does not require endogenous Ras or PKCs and probably occurs through a PMA-induced recruitment of gamma/Raf to the plasma membrane. The impaired ability of EGF to activate the Raf zinc finger variants in situ is attributable, at least in part, to a major decrement in their binding to Ras-GTP; both Raf zinc finger variants exhibit decreased association with Ras (V12) in situ upon coexpression in COS cells, as well as diminished binding in vitro to immobilized, processed COS recombinant Ras(V12)-GTP. In contrast, Raf binding to unprocessed COS or prokaryotic recombinant Ras-GTP is unaffected by Raf zinc finger mutation. Thus, the Raf zinc finger contributes an important component ...Continue Reading

References

Jul 30, 1992·Nature·J M KyriakisJ Avruch
Dec 1, 1985·Molecular and Cellular Biology·G I EvanJ M Bishop
Jun 9, 1995·The Journal of Biological Chemistry·Y H ChowR Jove
Oct 6, 1995·The Journal of Biological Chemistry·Z J LuoJ Avruch
Apr 28, 1995·The Journal of Biological Chemistry·T R BrtvaC J Der
Jul 1, 1994·Trends in Biochemical Sciences·J AvruchJ M Kyriakis
Jul 1, 1993·Trends in Biochemical Sciences·M S Marshall
Jan 5, 1996·The Journal of Biological Chemistry·J K DruganS L Campbell
May 17, 1996·The Journal of Biological Chemistry·C MineoR G Anderson
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·H R MottS L Campbell

❮ Previous
Next ❯

Citations

Apr 1, 2015·The Journal of Cell Biology·Devinderjit K MoudgilGordon K T Chan
Mar 1, 2000·British Journal of Pharmacology·G LenzJ T Neary
Jan 31, 2013·Biochimica Et Biophysica Acta·Deborah T LeichtGuri Tzivion
Jun 9, 2007·Biochimica Et Biophysica Acta·Deborah T LeichtGuri Tzivion
Feb 6, 2007·Biochimica Et Biophysica Acta·John M Kyriakis
Aug 25, 2001·Annual Review of Neuroscience·M V SofroniewW C Mobley
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·N R MichaudD K Morrison
Apr 5, 2002·Molecular Carcinogenesis·Edmond Y W ChanJames C Stone
Mar 26, 1998·Journal of Cellular Biochemistry·O M TsygankovaJ R Williamson
Dec 13, 2003·The Journal of Biological Chemistry·Jennifer A ClarkJennifer D Black
Mar 10, 2004·Oncogene·Yumi AoyamaXian-Feng Zhang
Jul 23, 2002·Molecular Biology of the Cell·Tzvetanka BondevaTamas Balla
Aug 13, 1999·Oncogene·R A McPhersonJ F Hancock
Oct 29, 1999·European Journal of Biochemistry·I RubioR Wetzker
Oct 11, 2001·Biological Chemistry·M VölkertH Waldmann
Nov 2, 2018·Biochemical Society Transactions·Soheila Rezaei AdarianiMohammad Reza Ahmadian
Jan 24, 2018·Cold Spring Harbor Perspectives in Medicine·Elizabeth M Terrell, Deborah K Morrison
May 15, 2007·Oncogene·A Clapéron, M Therrien
Apr 25, 2015·Nature Reviews. Molecular Cell Biology·Hugo Lavoie, Marc Therrien
Sep 8, 2010·Cellular and Molecular Life Sciences : CMLS·Christian M UdellMarc Therrien
Oct 19, 2011·Future Medicinal Chemistry·Antonio T BainesChanning J Der
Jan 17, 2020·Cells·Ufuk DegirmenciJiancheng Hu
Oct 24, 2000·Oncogene·C BondziG W Krystal
Feb 6, 1999·The Journal of Biological Chemistry·A D LairdD Shalloway
Aug 15, 1998·The Journal of Biological Chemistry·D G WinklerJ A Cooper
Aug 8, 1997·The Journal of Biological Chemistry·S RoyJ F Hancock
Mar 20, 1999·The Journal of Biological Chemistry·V NancyJ de Gunzburg
Apr 25, 2000·The Journal of Biological Chemistry·J G WilliamsS L Campbell
May 10, 2000·The Journal of Biological Chemistry·M A BoodenJ E Buss
Apr 25, 2002·The Journal of Biological Chemistry·Beatrice HoyosUlrich Hammerling
Mar 19, 2003·The Journal of Biological Chemistry·Tara L BakerJanice E Buss
Mar 2, 2006·Molecular and Cellular Biology·Linda K RushworthWalter Kolch

❮ 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.