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PMID: 2841581 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The first seven amino acids encoded by the v-src oncogene act as a myristylation signal: lysine 7 is a critical determinant.

Molecular and cellular biology ·Vol. 8 ·No. 6 ·1988-06-00 ·Pages 2435-41

Kaplan JM, Mardon G, Bishop JM, Varmus HE

Abstract

The transforming protein of Rous sarcoma virus, pp60v-src, is covalently coupled to myristic acid by an amide linkage to glycine 2. Myristylation promotes the association of pp60v-src with cellular membranes, and this subcellular location is essential for transforming activity. The findings presented here, in conjunction with the previous reports of others, imply that the seventh amino acid encoded by v-src might be important in the myristylation reaction. Replacement of lysine 7 by asparagine greatly reduced the myristylation, membrane association, and transforming activity of pp60v-src. In contrast, substitution of arginine at residue 7 had no effect on any of these properties of pp60v-src. Addition of amino acids 1 to 7 encoded by v-src was sufficient to cause myristylation of a src-pyruvate kinase fusion protein. We conclude that the recognition sequence for myristylation of pp60v-src comprises amino acids 1 to 7 and that lysine 7 is a critical component of this sequence.

MeSH Terms
Acylation Amino Acid Sequence Animals Antibodies, Monoclonal/immunology Avian Sarcoma Viruses/genetics Cells, Cultured Chick Embryo Electrophoresis, Polyacrylamide Gel Fibroblasts/microbiology Lysine/analysis Myristic Acid Myristic Acids/metabolism Oncogene Protein pp60(v-src) Protein Kinases/analysis,metabolism Retroviridae Proteins/analysis,immunology,metabolism
Chemicals
Antibodies, Monoclonal Myristic Acids Retroviridae Proteins Myristic Acid Protein Kinases Oncogene Protein pp60(v-src) Lysine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kaplan J M
Department of Microbiology, University of California, San Francisco 94143.
Mardon G
Bishop J M
Varmus H E
References (53)
53 references, click to expand
  1. n-Tetradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle.
    Proc Natl Acad Sci U S A. 1982 Oct;79(20):6128-31 PMID: 6959104
  2. The structure and protein kinase activity of proteins encoded by nonconditional mutants and back mutants in the sec gene of avian sarcoma virus.
    Virology. 1981 Jan 15;108(1):47-70 PMID: 6267776
  3. Identification of the NH2-terminal blocking group of calcineurin B as myristic acid.
    FEBS Lett. 1982 Dec 27;150(2):314-8 PMID: 7160476
  4. Nucleotide sequence of Rous sarcoma virus.
    Cell. 1983 Mar;32(3):853-69 PMID: 6299578
  5. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus.
    Cell. 1983 Mar;32(3):881-90 PMID: 6299580
  6. Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification.
    Proc Natl Acad Sci U S A. 1983 Jan;80(2):339-43 PMID: 6340098
  7. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses.
    J Virol. 1983 Nov;48(2):352-60 PMID: 6312092
  8. Subcellular localization of pp60src in RSV-transformed cells.
    Curr Top Microbiol Immunol. 1983;107:51-124 PMID: 6321110
  9. Identification of the NH2-terminal blocking group of NADH-cytochrome b5 reductase as myristic acid and the complete amino acid sequence of the membrane-binding domain.
    J Biol Chem. 1984 Nov 10;259(21):13349-54 PMID: 6436247
  10. Cellular localization of c-fps gene product NCP98.
    J Virol. 1984 Dec;52(3):913-8 PMID: 6092720
  11. Changes in amino-terminal sequences of pp60src lead to decreased membrane association and decreased in vivo tumorigenicity.
    Cell. 1982 Apr;28(4):889-96 PMID: 6284379
  12. Site-directed mutagenesis of the src gene of Rous sarcoma virus: construction and characterization of a deletion mutant temperature sensitive for transformation.
    J Virol. 1982 Nov;44(2):683-91 PMID: 6292526
  13. Amino-terminal processing of proteins by N-myristoylation. Substrate specificity of N-myristoyl transferase.
    J Biol Chem. 1987 Jan 25;262(3):1030-6 PMID: 3100524
  14. The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck.
    Mol Cell Biol. 1987 Jan;7(1):237-43 PMID: 3561390
  15. Characterization of cDNA clones for the human c-yes gene.
    Mol Cell Biol. 1987 Jan;7(1):41-7 PMID: 2436037
  16. Myristic acid is coupled to a structural protein of polyoma virus and SV40.
    Nature. 1987 Apr 9-15;326(6113):619-22 PMID: 3031509
  17. The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid.
    J Virol. 1987 May;61(5):1672-7 PMID: 3573147
  18. Structure of the feline c-fes/fps proto-oncogene: genesis of a retroviral oncogene.
    J Virol. 1987 Jun;61(6):2009-16 PMID: 3553615
  19. Purification and characterization of yeast myristoyl CoA:protein N-myristoyltransferase.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2708-12 PMID: 3106975
  20. Myristylation of picornavirus capsid protein VP4 and its structural significance.
    Nature. 1987 Jun 11-17;327(6122):482-6 PMID: 3035380
  21. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells.
    Mol Cell Biol. 1987 Jun;7(6):2267-75 PMID: 3496523
  22. Acylation of proteins with myristic acid occurs cotranslationally.
    Science. 1987 Nov 27;238(4831):1275-8 PMID: 3685978
  23. Primary structure of the human fgr proto-oncogene product p55c-fgr.
    Mol Cell Biol. 1988 Jan;8(1):259-66 PMID: 3275868
  24. Myristoyl CoA:protein N-myristoyltransferase activities from rat liver and yeast possess overlapping yet distinct peptide substrate specificities.
    J Biol Chem. 1988 Feb 5;263(4):1784-90 PMID: 3123478
  25. Characteristics of an assay for Rous sarcoma virus and Rous sarcoma cells in tissue culture.
    Virology. 1958 Dec;6(3):669-88 PMID: 13616179
  26. Biological properties of human c-Ha-ras1 genes mutated at codon 12.
    Nature. 1984 Nov 1-7;312(5989):71-5 PMID: 6092966
  27. A short amino acid sequence able to specify nuclear location.
    Cell. 1984 Dec;39(3 Pt 2):499-509 PMID: 6096007
  28. Myristic acid, a rare fatty acid, is the lipid attached to the transforming protein of Rous sarcoma virus and its cellular homolog.
    J Virol. 1985 Jan;53(1):7-12 PMID: 2981363
  29. Covalently bound myristate in a lymphoma tyrosine protein kinase.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7679-82 PMID: 6595656
  30. Amino terminal myristylation of the protein kinase p60src, a retroviral transforming protein.
    Science. 1985 Jan 25;227(4685):427-9 PMID: 3917576
  31. Specificity of fatty acid acylation of cellular proteins.
    J Biol Chem. 1985 Mar 25;260(6):3784-90 PMID: 3972848
  32. Myristic acid is attached to the transforming protein of Rous sarcoma virus during or immediately after synthesis and is present in both soluble and membrane-bound forms of the protein.
    Mol Cell Biol. 1984 Dec;4(12):2697-704 PMID: 6441887
  33. An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins.
    Nature. 1985 Mar 28-Apr 3;314(6009):374-7 PMID: 3920530
  34. Fine structural mapping of a critical NH2-terminal region of p60src.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623-7 PMID: 2984663
  35. Two classes of fatty acid acylated proteins exist in eukaryotic cells.
    EMBO J. 1985 May;4(5):1137-44 PMID: 2988939
  36. Studies on the attachment of myristic and palmitic acid to cell proteins in human squamous carcinoma cell lines: evidence for two pathways.
    EMBO J. 1985 May;4(5):1145-52 PMID: 4006909
  37. Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation.
    Proc Natl Acad Sci U S A. 1985 Jul;82(14):4625-8 PMID: 2991884
  38. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA.
    Cell. 1985 Dec;43(2 Pt 1):393-404 PMID: 2416464
  39. Fatty acylation of cellular proteins. Temporal and subcellular differences between palmitate and myristate acylation.
    J Biol Chem. 1986 Feb 15;261(5):2458-66 PMID: 3944142
  40. The absence of myristic acid decreases membrane binding of p60src but does not affect tyrosine protein kinase activity.
    J Virol. 1986 May;58(2):468-74 PMID: 3009860
  41. Protein fatty acid acylation: enzymatic synthesis of an N-myristoylglycyl peptide.
    Proc Natl Acad Sci U S A. 1986 May;83(9):2812-6 PMID: 3517877
  42. Processing of p60v-src to its myristylated membrane-bound form.
    Mol Cell Biol. 1985 Oct;5(10):2781-8 PMID: 3016513
  43. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459-63 PMID: 3526330
  44. Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene.
    Cell. 1986 Oct 24;47(2):277-84 PMID: 3021337
  45. NH2-terminal sequences of two src proteins that cause aberrant transformation.
    Proc Natl Acad Sci U S A. 1987 Jan;84(1):80-4 PMID: 3025866
  46. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  47. Identification of a transformation-specific antigen induced by an avian sarcoma virus.
    Nature. 1977 Sep 22;269(5626):346-8 PMID: 198667
  48. Virus-specific messenger RNAs in permissive cells infected by avian sarcoma virus.
    J Biol Chem. 1979 Aug 25;254(16):8015-22 PMID: 224042
  49. Evidence that the src gene product of Rous sarcoma virus is membrane associated.
    Virology. 1980 Feb;101(1):25-40 PMID: 6243822
  50. Adhesion plaques of Rous sarcoma virus-transformed cells contain the src gene product.
    Proc Natl Acad Sci U S A. 1980 Jun;77(6):3514-8 PMID: 6251464
  51. The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):3783-7 PMID: 6253989
  52. Revertants of an ASV-transformed rat cell line have lost the complete provius or sustained mutations in src.
    Virology. 1981 Jan 15;108(1):28-46 PMID: 6168094
  53. Transit of pp60v-src to the plasma membrane.
    Proc Natl Acad Sci U S A. 1982 Dec;79(23):7117-21 PMID: 6296817
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1988-06-00
Pages
2435-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363442
Subset
IM
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