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Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding.

Publication ,  Journal Article
Fukasawa, K; Zhou, R; Matten, WT; Armstrong, AJ; Daar, I; Oskarsson, M; Sathyanarayana, BK; Maclvor, L; Wood, TG; Vande Woude, GF
Published in: Oncogene
October 19, 1995

We constructed in-frame deletion/replacement mutations in the Xenopus mos proto-oncogene that lie within conserved Mos-specific codons, but outside of the regions that are conserved among the src kinase family of genes. All gene products were assayed in vitro for kinase activity and in vivo for their ability to induce oocyte maturation, embryonic cleavage arrest and cellular transformation. Most mutations in Mos eliminated both kinase and biological activity. However, a mutation in Mos that removed two basic amino acid residues (R94 and K97) downstream from the lysine at the ATP binding site (K90) markedly enhanced autophosphorylation activity. Moreover, this mutant displayed markedly reduced biological activity, lacked transforming activity, and failed to activate mitogen activated protein kinase (MAPK). A second mutant Mos product, lacking amino acids R45-A54, displayed a five-fold increase in cellular transforming activity. This Mos mutant specifically localized to the cytoplasm; in contrast to wild-type (wt) Mos that localized to both the nucleus and the cytoplasm. These data indicate that Mos transforming activity is mediated via signalling exerted in the cytoplasm, presumably through MAPK, and that nuclear localization of the oncogene product interferes with transforming activity. We also show that amino acids R45-A54 are important for Mos DNA binding activity.

Duke Scholars

Published In

Oncogene

ISSN

0950-9232

Publication Date

October 19, 1995

Volume

11

Issue

8

Start / End Page

1447 / 1457

Location

England

Related Subject Headings

  • Xenopus laevis
  • Structure-Activity Relationship
  • Signal Transduction
  • Sequence Deletion
  • Proto-Oncogene Proteins c-mos
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Oocytes
  • Oncology & Carcinogenesis
  • Mutagenesis, Site-Directed
 

Citation

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MLA
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Fukasawa, K., Zhou, R., Matten, W. T., Armstrong, A. J., Daar, I., Oskarsson, M., … Vande Woude, G. F. (1995). Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding. Oncogene, 11(8), 1447–1457.
Fukasawa, K., R. Zhou, W. T. Matten, A. J. Armstrong, I. Daar, M. Oskarsson, B. K. Sathyanarayana, L. Maclvor, T. G. Wood, and G. F. Vande Woude. “Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding.Oncogene 11, no. 8 (October 19, 1995): 1447–57.
Fukasawa K, Zhou R, Matten WT, Armstrong AJ, Daar I, Oskarsson M, et al. Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding. Oncogene. 1995 Oct 19;11(8):1447–57.
Fukasawa K, Zhou R, Matten WT, Armstrong AJ, Daar I, Oskarsson M, Sathyanarayana BK, Maclvor L, Wood TG, Vande Woude GF. Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding. Oncogene. 1995 Oct 19;11(8):1447–1457.

Published In

Oncogene

ISSN

0950-9232

Publication Date

October 19, 1995

Volume

11

Issue

8

Start / End Page

1447 / 1457

Location

England

Related Subject Headings

  • Xenopus laevis
  • Structure-Activity Relationship
  • Signal Transduction
  • Sequence Deletion
  • Proto-Oncogene Proteins c-mos
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Oocytes
  • Oncology & Carcinogenesis
  • Mutagenesis, Site-Directed