Human Retroviral gag- and gag-pol-like Proteins Interact with the Transforming Growth Factor-β Receptor Activin Receptor-like Kinase 1

TY - JOUR

T1 - Human Retroviral gag- and gag-pol-like Proteins Interact with the Transforming Growth Factor-β Receptor Activin Receptor-like Kinase 1

AU - Lux, Andreas

AU - Beil, Christian

AU - Majety, Meher

AU - Barron, Suzanne

AU - Gallione, Carol J.

AU - Kuhn, Hella-Monika

AU - Berg, Jonathan N.

AU - Kioschis, Petra

AU - Marchuk, Douglas A.

AU - Hafner, Mathias

PY - 2005/3/4

Y1 - 2005/3/4

N2 - Mutations in activin receptor-like kinase 1 (ALK1), a transforming growth factor (TGF)-β 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-β 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-β receptor family.

AB - Mutations in activin receptor-like kinase 1 (ALK1), a transforming growth factor (TGF)-β 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-β 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-β receptor family.

UR - https://www.scopus.com/pages/publications/20044376656

U2 - 10.1074/jbc.M409197200

DO - 10.1074/jbc.M409197200

M3 - Article

C2 - 15611116

AN - SCOPUS:20044376656

SN - 0021-9258

VL - 280

SP - 8482

EP - 8493

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 9

ER -