Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product

Matthew J Hart, Alessandra Eva, Daniela Zangrilli, Stuart A. Aaronson, Tony Evans, Richard A. Cerione, Yi Zheng

Research output: Contribution to journalArticle

271 Citations (Scopus)

Abstract

The dbl oncogene product contains a 238-amino acid domain, which is shared by an expanding family of growth regulatory proteins. These include the Saccharomyces cerevisiae cell division cycle protein, CDC24, the breakpoint cluster region protein, the ect2 and vav oncogene products, and the brain GDP-releasing factor for Ras. Previous studies have provided evidence that oncogenic Dbl or an associated protein stimulates GDP dissociation from the human species (Hs) homolog of CDC42. We show here that Dbl specifically complexes with the GDP-bound forms of CDC42Hs and RhoA, but not Rac1 or TC10, and that this specificity correlates with the ability of Dbl to act as a GDP- releasing factor. Small deletions throughout the Dbl domain, which inactivate transformation, eliminated the ability of Dbl to stimulate GDP dissociation, whereas deletions outside of this domain did not impair either function. Finally, the Dbl domain itself, when expressed and purified as a recombinant protein, was shown to stimulate GDP dissociation from purified, recombinant CDC42Hs. These findings establish that a minimal unit on Dbl that is critical to its transforming function directly regulates GDP-GTP exchange activity.

Original languageEnglish (US)
Pages (from-to)62-65
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number1
StatePublished - Jan 7 1994
Externally publishedYes

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Guanine Nucleotides
Oncogene Proteins
Proto-Oncogene Proteins c-bcr
Saccharomyces cerevisiae Proteins
Cell Cycle Proteins
Guanosine Triphosphate
Recombinant Proteins
Proteins
Amino Acids
Yeast
Brain
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hart, M. J., Eva, A., Zangrilli, D., Aaronson, S. A., Evans, T., Cerione, R. A., & Zheng, Y. (1994). Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. Journal of Biological Chemistry, 269(1), 62-65.

Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. / Hart, Matthew J; Eva, Alessandra; Zangrilli, Daniela; Aaronson, Stuart A.; Evans, Tony; Cerione, Richard A.; Zheng, Yi.

In: Journal of Biological Chemistry, Vol. 269, No. 1, 07.01.1994, p. 62-65.

Research output: Contribution to journalArticle

Hart, MJ, Eva, A, Zangrilli, D, Aaronson, SA, Evans, T, Cerione, RA & Zheng, Y 1994, 'Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product', Journal of Biological Chemistry, vol. 269, no. 1, pp. 62-65.
Hart, Matthew J ; Eva, Alessandra ; Zangrilli, Daniela ; Aaronson, Stuart A. ; Evans, Tony ; Cerione, Richard A. ; Zheng, Yi. / Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 1. pp. 62-65.
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