Search tips
Search criteria 


Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1989 June; 9(6): 2724–2727.
PMCID: PMC362345

Transformation of NIH 3T3 fibroblasts by an activated form of p59hck.


Phosphorylation of a tyrosine residue near the carboxy terminus of src-family protein tyrosine kinases is believed to regulate the biological activity of these gene products. Conversion of this tyrosine in p59hck (Tyr-501) to a phenylalanine residue by using oligonucleotide-directed mutagenesis yielded a product (p59hckF501) with very potent transforming activity. Quantitative analysis by a soft-agar cloning assay revealed that p59hckF501 was more than 100-fold more effective than a closely related transforming element, p56lckF505, in colony formation. Cells bearing p59hckF501 had increased levels of protein phosphotyrosine. The ability of p59hckF501 to transform NIH 3T3 cells was abolished by a second mutation believed to destroy the ATP-binding domain.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (894K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Amrein KE, Sefton BM. Mutation of a site of tyrosine phosphorylation in the lymphocyte-specific tyrosine protein kinase, p56lck, reveals its oncogenic potential in fibroblasts. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4247–4251. [PubMed]
  • Bishop JM. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. [PubMed]
  • Cartwright CA, Eckhart W, Simon S, Kaplan PL. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell. 1987 Apr 10;49(1):83–91. [PubMed]
  • Cooper JA, Gould KL, Cartwright CA, Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. [PubMed]
  • Cooper JA, King CS. Dephosphorylation or antibody binding to the carboxy terminus stimulates pp60c-src. Mol Cell Biol. 1986 Dec;6(12):4467–4477. [PMC free article] [PubMed]
  • Cooper JA, MacAuley A. Potential positive and negative autoregulation of p60c-src by intermolecular autophosphorylation. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4232–4236. [PubMed]
  • Huhn RD, Posner MR, Rayter SI, Foulkes JG, Frackelton AR., Jr Cell lines and peripheral blood leukocytes derived from individuals with chronic myelogenous leukemia display virtually identical proteins phosphorylated on tyrosine residues. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4408–4412. [PubMed]
  • Hunter T, Cooper JA. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. [PubMed]
  • Kamps MP, Taylor SS, Sefton BM. Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites. Nature. 1984 Aug 16;310(5978):589–592. [PubMed]
  • Kmiecik TE, Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. [PubMed]
  • Mann R, Mulligan RC, Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. [PubMed]
  • Marth JD, Cooper JA, King CS, Ziegler SF, Tinker DA, Overell RW, Krebs EG, Perlmutter RM. Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck). Mol Cell Biol. 1988 Feb;8(2):540–550. [PMC free article] [PubMed]
  • Perlmutter RM, Marth JD, Ziegler SF, Garvin AM, Pawar S, Cooke MP, Abraham KM. Specialized protein tyrosine kinase proto-oncogenes in hematopoietic cells. Biochim Biophys Acta. 1989 Feb;948(3):245–262. [PubMed]
  • Piwnica-Worms H, Saunders KB, Roberts TM, Smith AE, Cheng SH. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. [PubMed]
  • Quintrell N, Lebo R, Varmus H, Bishop JM, Pettenati MJ, Le Beau MM, Diaz MO, Rowley JD. 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):2267–2275. [PMC free article] [PubMed]
  • Reynolds AB, Vila J, Lansing TJ, Potts WM, Weber MJ, Parsons JT. Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus. EMBO J. 1987 Aug;6(8):2359–2364. [PubMed]
  • Scher CD, Siegler R. Direct transformation of 3T3 cells by Abelson murine leukaemia virus. Nature. 1975 Feb 27;253(5494):729–731. [PubMed]
  • Stahl ML, Ferenz CR, Kelleher KL, Kriz RW, Knopf JL. Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988 Mar 17;332(6161):269–272. [PubMed]
  • Testa JR, Kinnealey A, Rowley JD, Golde DW, Potter D. Deletion of the long arm of chromosome 20 [del(20)(q11)] in myeloid disorders. Blood. 1978 Nov;52(5):868–877. [PubMed]
  • Ziegler SF, Marth JD, Lewis DB, Perlmutter RM. Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin. Mol Cell Biol. 1987 Jun;7(6):2276–2285. [PMC free article] [PubMed]
  • Ziegler SF, Wilson CB, Perlmutter RM. Augmented expression of a myeloid-specific protein tyrosine kinase gene (hck) after macrophage activation. J Exp Med. 1988 Nov 1;168(5):1801–1810. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)