Identification of Tctex2β, a novel dynein light chain family member that interacts with different transforming growth factor-β receptors

John Mccarthy, QingJun Meng, Andreas Lux, Andreas Holloschi, Jian Li, John M X Hughes, Tassilo Foerg, John E G McCarthy, Anthony M. Heagerty, Petra Kioschis, Mathias Hafner, John M. Garland

    Research output: Contribution to journalArticlepeer-review


    Endoglin is a membrane-inserted protein that is preferentially synthesized in angiogenic vascular endothelial and smooth muscle cells. Endoglin associates with members of the transforming growth factor-β (TGF-β) receptor family and has been identified as the gene involved in hereditary hemorrhagic telangiectasia. Although endoglin is known to affect cell responses to TGF-β, its mode of action is largely unknown. We performed yeast two-hybrid screening of a human placental cDNA library and isolated a new endoglin-binding partner, a novel 221-amino acid member of the Tctex1/2 family of cytoplasmic dynein light chains named Tctex2β, as the founder of a new Tctex1/2 subfamily. The interaction was localized exclusively to the cytoplasmic domain of endoglin. Reverse transcription-PCR showed expression of Tctex2β in a wide range of tissues, including vascular endothelial and smooth muscle cells, placenta, and testis, as well as in several tumor cell lines. High expression levels were found in human umbilical vein endothelial cells and the large cell lung cancer cell line. Forced expression of Tctex2β had a profound inhibitory effect on TGF-β signaling. Additional Tctex2β-interacting receptors were identified to be the TGF-β type II receptor and most likely beta-glycan, but not ALK5, ALK1, or the bone morphogenetic protein type II receptor. Upon fluorescence tagging, co-localization of Tctex2β and endoglin, as well as Tctex2β, endoglin, and the TGF-β type II receptor, was observed by different microscopy techniques. Our findings link endoglin for the first time to microtubule-based minus end-directed transport machinery, suggesting that some endoglin functions might be regulated and directed by its interaction with the cytoplasmic dynein light chain Tctex2β. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)37069-37080
    Number of pages11
    JournalJournal of Biological Chemistry
    Issue number48
    Publication statusPublished - 1 Dec 2006


    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • metabolism: Bone Morphogenetic Protein Receptors, Type II
    • COS Cells
    • chemistry: Carrier Proteins
    • Cercopithecus aethiops
    • chemistry: Drosophila Proteins
    • Humans
    • Mice
    • physiology: Microtubule-Associated Proteins
    • Mink
    • Molecular Sequence Data
    • NIH 3T3 Cells
    • physiology: Nuclear Proteins
    • Phylogeny
    • Protein Binding
    • metabolism: Receptors, Transforming Growth Factor beta
    • Sequence Homology, Amino Acid


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