This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Courtois, G. Articles by Gisselbrecht, S. Search for Related Content PubMed PubMed Citation Articles by Courtois, G. Articles by Gisselbrecht, S.

 Previous Article  |  Next Article 

J. Virol., 05 1995, 2794-2800, Vol 69, No. 5
Copyright © 1995, American Society for Microbiology

Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization

G Courtois, L Benit, Y Mikaeloff, M Pauchard, M Charon, P Varlet and S Gisselbrecht
Institut Cochin de Genetique Moleculaire, Institut National de la Sante et de la Recherche Medicale, Universite Paris V, Hopital Cochin, France.

The myeloproliferative leukemia retrovirus (MPLV) has the v-mpl cellular sequences transduced in frame with the deleted and rearranged Friend murine leukemia virus env gene. The resulting env-mpl fusion oncogene is responsible for an acute myeloproliferative disorder induced in mice by MPLV. v-mpl is a truncated form of the c-mpl gene which encodes the receptor for thrombopoietin. We investigated the contribution of the Env-Mpl extracellular domain in the constitutive activation of this truncated cytokine receptor and found that the rearrangement of the env sequences in the env-mpl fusion gene was not required for oncogenicity. A pathogenic variant, DEL3MPLV, was generated, which differs from MPLV by the deletions of 22 amino acids of the Env signal peptide, all of the mature Env sequences, and 18 N- terminal amino acids of the v-Mpl extracellular domain. The resulting del3-mpl oncogene product conserves in its extracellular region the first 12 amino acids of the Env signal sequence including a cysteine residue, and 25 amino acids of the v-Mpl. We show here that a mutation converting this cysteine to a glycine completely abolishes del3-mpl oncogenicity and that the del3-mpl oncogene product is constitutively activated by disulfide-linked homodimerization.

This article has been cited by other articles:

• Meunier, C., Bordereaux, D., Porteu, F., Gisselbrecht, S., Chretien, S., Courtois, G. (2002). Cloning and Characterization of a Family of Proteins Associated with Mpl. J. Biol. Chem. 277: 9139-9147 [Abstract] [Full Text]  
• Letestu, R., Vitrat, N., Masse, A., Couedic, J.-P. L., Lazar, V., Rameau, P., Wendling, F., Vuillier, J., Boutard, P., Plouvier, E., Plasse, M., Favier, R., Vainchenker, W., Debili, N. (2000). Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome. Blood 95: 1633-1641 [Abstract] [Full Text]  
• Drachman, J. G., Millett, K. M., Kaushansky, K. (1999). Thrombopoietin Signal Transduction Requires Functional JAK2, Not TYK2. J. Biol. Chem. 274: 13480-13484 [Abstract] [Full Text]  
• Liu, R. Y., Fan, C., Garcia, R., Jove, R., Zuckerman, K. S. (1999). Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines. Blood 93: 2369-2379 [Abstract] [Full Text]  
• Gonda, T. J., D'Andrea, R. J. (1997). Activating Mutations in Cytokine Receptors: Implications for Receptor Function and Role in Disease. Blood 89: 355-369 [Full Text]