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Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.

Publication ,  Journal Article
Lux, A; Beil, C; Majety, M; Barron, S; Gallione, CJ; Kuhn, H-M; Berg, JN; Kioschis, P; Marchuk, DA; Hafner, M
Published in: J Biol Chem
March 4, 2005

Mutations in activin receptor-like kinase 1 (ALK1), a transforming growth factor (TGF)-beta type I receptor, lead to the vascular disorder hereditary hemorrhagic telangiectasia caused by abnormal vascular remodeling. The underlying molecular cause of this disease is not well understood. Identifying binding partners for ALK1 will help to understand its cellular function. Using the two-hybrid system, we identified an ALK1-binding protein encoded by an ancient retroviral/retrotransposon element integrated as a single copy gene known as PEG10 on human chromosome 7q21. PEG10 contains two overlapping reading frames from which two proteins, PEG10-RF1 and PEG10-RF1/2, are translated by a typical retroviral -1 ribosomal frameshift mechanism. Reverse transcription-PCR and Northern blot analysis showed a broad range of PEG10 expression in different tissues and cell types, i.e. human placenta, brain, kidney, endothelial cells, lymphoblasts, and HepG2 and HEK293 cells. However, endogenous PEG10-RF1 and PEG10-RF1/2 proteins were only detected in HepG2 and HEK293 cells. PEG10-RF1, which is the major PEG10 protein product, represents a gag-like protein, and PEG10-RF1/2 represents a gag-pol-like protein. PEG10-RF1 also interacts with different members of TGF-beta superfamily type I and II receptors. PEG10-RF1 binding to ALK1 is mediated by a 200-amino acid domain with no recognized motif. PEG10-RF1 inhibits ALK1 as well as ALK5 signaling. Co-expression of ALK1 and PEG10-RF1 in different cell types induced morphological changes reminiscent of neuronal cells or sprouting cells. This is the first report of a human retroviral-like protein interacting with members of the TGF-beta receptor family.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 4, 2005

Volume

280

Issue

9

Start / End Page

8482 / 8493

Location

United States

Related Subject Headings

  • U937 Cells
  • Two-Hybrid System Techniques
  • Transforming Growth Factor beta
  • Transfection
  • Tissue Distribution
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retroviridae
  • Protein Structure, Tertiary
  • Protein Binding
 

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Lux, A., Beil, C., Majety, M., Barron, S., Gallione, C. J., Kuhn, H.-M., … Hafner, M. (2005). Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1. J Biol Chem, 280(9), 8482–8493. https://doi.org/10.1074/jbc.M409197200
Lux, Andreas, Christian Beil, Meher Majety, Suzanne Barron, Carol J. Gallione, Hella-Monika Kuhn, Jonathan N. Berg, Petra Kioschis, Douglas A. Marchuk, and Mathias Hafner. “Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.J Biol Chem 280, no. 9 (March 4, 2005): 8482–93. https://doi.org/10.1074/jbc.M409197200.
Lux A, Beil C, Majety M, Barron S, Gallione CJ, Kuhn H-M, et al. Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1. J Biol Chem. 2005 Mar 4;280(9):8482–93.
Lux, Andreas, et al. “Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.J Biol Chem, vol. 280, no. 9, Mar. 2005, pp. 8482–93. Pubmed, doi:10.1074/jbc.M409197200.
Lux A, Beil C, Majety M, Barron S, Gallione CJ, Kuhn H-M, Berg JN, Kioschis P, Marchuk DA, Hafner M. Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1. J Biol Chem. 2005 Mar 4;280(9):8482–8493.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 4, 2005

Volume

280

Issue

9

Start / End Page

8482 / 8493

Location

United States

Related Subject Headings

  • U937 Cells
  • Two-Hybrid System Techniques
  • Transforming Growth Factor beta
  • Transfection
  • Tissue Distribution
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retroviridae
  • Protein Structure, Tertiary
  • Protein Binding