Site-directed mutagenesis of the SH2- and SH3-coding domains of c-src produces varied phenotypes, including oncogenic activation of p60c-src.

Molecular and Cellular Biology
H Hirai, H Varmus

Abstract

The products of the viral and cellular src genes, p60v-src and p60c-src, appear to be composed of multiple functional domains. Highly conserved regions called src homology 2 and 3 (SH2 and SH3), comprising amino acid residues 88 to 250, are believed to modulate the protein-tyrosine kinase activity present in the carboxy-terminal halves of the src proteins. To explore the functions of these regions more fully, we have made 34 site-directed mutations in a transformation-competent c-src gene encoding phenylalanine in place of tyrosine 527 (Y527F c-src). Twenty of the new mutations change only one or two amino acids, and the remainder delete small or large portions of the SH2-SH3 region. These mutant alleles have been incorporated into a replication-competent Rous sarcoma virus vector to examine the biochemical and biological properties of the mutant proteins after infection of chicken embryo fibroblasts. Four classes of mutant proteins were observed: class 1, mutants with only slight differences from the parental gene products; class 2, mutant proteins with diminished transforming and specific kinase activities; class 3, mutant proteins with normal or enhanced specific kinase activity but impaired biological activity, often as a c...Continue Reading

References

Feb 1, 1979·Journal of Virology·G E HoutsJ W Beard
Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J B LevyH Hanafusa
Jan 1, 1987·Annual Review of Cell Biology·R Jove, H Hanafusa
Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·D PellmanH Hanafusa
Jan 1, 1985·Annual Review of Biochemistry·T Hunter, J A Cooper
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J E DeClueT Pawson
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Mar 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·A D LevinsonJ M Bishop

❮ Previous
Next ❯

Citations

Mar 1, 1994·Cancer Metastasis Reviews·S H Lo, L B Chen
Sep 5, 1997·The Journal of Biological Chemistry·M Y KanemitsuW Eckhart
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·A WeijlandG Superti-Furga
Apr 26, 2001·The Journal of Biological Chemistry·K M Smith, R A Van Etten
Mar 15, 2006·Critical Reviews in Clinical Laboratory Sciences·Hellinida Thomadaki, Andreas Scorilas
Oct 7, 2015·Frontiers in Immunology·Zachary J GerbecSubramaniam Malarkannan
Jan 6, 1995·The Journal of Biological Chemistry·C S Abrams, W Zhao
Apr 1, 1994·Immunological Reviews·D J Rawlings, O N Witte
Apr 12, 1996·The Journal of Biological Chemistry·T NakamotoH Hirai
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·K F HarrisP M Howley
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Miles A Pufall, Barbara J Graves
Dec 7, 2007·The Journal of Biological Chemistry·Silje Anette SolheimTorunn Berge
Aug 1, 1995·FEBS Letters·G Superti-Furga
Mar 8, 1996·The Journal of Biological Chemistry·H KawakatsuJ Yano
Jul 18, 1997·The Journal of Biological Chemistry·S D BriggsT E Smithgall
Dec 1, 1995·Molecular Reproduction and Development·D K Morrison
Feb 14, 1998·International Journal of Cancer. Journal International Du Cancer·G J DeichmanA V Gudkov
Feb 13, 2016·PloS One·Ming ZhaoKristiina Vuori
Jan 1, 1996·Progress in Biophysics and Molecular Biology·M Sudol
May 27, 2010·Journal of Cell Science·Diane ColelloSusan E LaFlamme
Jun 9, 2001·Archives of Biochemistry and Biophysics·D A Henriques, J E Ladbury
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
Dec 1, 1996·Cellular Signalling·F Romero, S Fischer
Jul 28, 1995·Biochimica Et Biophysica Acta·B Schaffhausen
Apr 1, 1997·The International Journal of Biochemistry & Cell Biology·J B Trager, G S Martin

❮ 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.