Identification of Tctex2β, a Novel Dynein Light Chain Family Member That Interacts with Different Transforming Growth Factor-β Receptors

Meng, Qing‐Jun; Lux, Andreas; Holloschi, Andreas; Li, Jian; Hughes, Juliette H.; Foerg, Tassilo; McCarthy, John E.G.; Heagerty, AM; Kioschis, Petra; Hafner, Mathias; Garland, John M.

doi:10.1074/jbc.m608614200

Cited by 41 publications

(41 citation statements)

References 47 publications

(50 reference statements)

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“…This interaction also occurs with the endoglin cytosolic domain and results in endoglin internalization with beta-arrestin2 in endocytic vesicles [Lee and Blobe, 2007]. Endoglin's cytosolic domain also interacts with a member of the Tctex1/2 family of cytosolic dynein light chains, Tctex2b, linking endoglin to the microtubule-based transport machinery [Meng et al, 2006]. Interestingly, Tctex1 is phosphorylated by the BMP type RII receptor, BMPRII [Machado et al, 2003] further supporting a functional linkage between Tctex proteins, endoglin, and TGFβ receptor complexes.…”

Section: Endoglin In Cell Adhesion and Migration: Role Of The Cytosolmentioning

confidence: 90%

“…This endoglin phosphorylation potentially regulates multiple protein-protein interactions involving the cytosolic domain. B: Endoglin interacts with the cytosolic proteins zyxin, ZRP-1, Tctex2b, and beta-arrestin [Conley et al, 2004;Sanz-Rodriguez et al, 2004;Koleva et al, 2006;Meng et al, 2006;Lee and Blobe, 2007]. These interactions likely mediate downstream functions, including F-actin dynamics, focal adhesion composition, and protein transport via endocytic vesicles.…”

Section: Endoglin and Vascular Smooth Muscle Cell Developmentmentioning

confidence: 99%

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Novel biochemical pathways of endoglin in vascular cell physiology

Bernabeu

Conley

Vary

2007

J of Cellular Biochemistry

119

123

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The broad role of the transforming growth factor beta (TGFβ) signaling pathway in vascular development, homeostasis, and repair is well appreciated. Endoglin is emerging as a novel, complex, and poorly understood regulatory component of the TGFβ receptor complex, whose importance is underscored by its recognition as the site of mutations causing hereditary hemorrhagic telangiectasia (HHT) [McAllister et al., 1994]. Extensive analyses of endoglin function in normal developmental mouse models [Bourdeau et al., 1999;Li et al., 1999;Arthur et al., 2000] and in HHT animal models [Bourdeau et al., 2000;Torsney et al., 2003] exemplify the importance of understanding endoglin's biochemical functions. However, novel mechanisms underlying the regulation of these pathways continue to emerge. These mechanisms include modification of TGFβ receptor signaling at the ligand and receptor activation level, direct effects of endoglin on cell adhesion and migration, and emerging roles for endoglin in the determination of stem cell fate and tissue patterning. The purpose of this review is to highlight the cellular and molecular studies that underscore the central role of endoglin in vascular development and disease. Keywords endoglin; transforming growth factor-beta receptors; hereditary hemorrhagic telangiectasia; vascular pathology; vascular endothelium; vascular smooth muscle The canonical transforming growth factor beta (TGFβ) signaling pathway comprises seven type I and five type II TGFβ receptors [Manning etal.,2002]. The TGFβ type I receptors are serine and threonine kinases, which include activin-like kinase 1 (ALK1) and TβRI, also known as ALK5. ALK1 and ALK5 associate with, and are activated via ligand-dependent phosphorylation [Vivien and Wrana, 1995] by the type II TGFβ receptor, TβRII [Wrana et al., 1992]. The activated type I receptor propagates canonical or Smad-dependent signals by phosphorylating Smad proteins [Shi and Massague, 2003;Feng and Derynck, 2005]. Another component of the TGFβ system is endoglin. Endoglin is a transmembrane protein [Gougos and Letarte, 1990] that acts as an auxiliary receptor for TGFβ [Cheifetz et al., 1992;Barbara et al., 1999]. Of note, mutations in endoglin (ENG) [McAllister et al., 1994] and ALK1 [Johnson et al., 1996] genes cause the vascular dysplasia hereditary hemorrhagic telangiectasia (HHT), termed HHT1 and HHT2, respectively.

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Section: Endoglin In Cell Adhesion and Migration: Role Of The Cytosolmentioning

confidence: 90%

Section: Endoglin and Vascular Smooth Muscle Cell Developmentmentioning

confidence: 99%

Novel biochemical pathways of endoglin in vascular cell physiology

Bernabeu

Conley

Vary

2007

J of Cellular Biochemistry

119

123

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“…km23-1 promotes both Smad-dependent (Jin et al 2007a) and Smad-independent signaling. In contrast, the motor protein dynein light chain Tctex2b associates with the short cytoplasmic tail of endoglin in endothelial cells and with TbRII and betaglycan in endothelial and other cell types, providing negative regulation of TGF-b signaling (Meng et al 2006). …”

Section: Cytoplasmic Kinases: Cgkimentioning

confidence: 99%

Signaling Receptors for TGF-β Family Members

Heldin

Moustakas

2016

Cold Spring Harb Perspect Biol

554

498

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Transforming growth factor b (TGF-b) family members signal via heterotetrameric complexes of type I and type II dual specificity kinase receptors. The activation and stability of the receptors are controlled by posttranslational modifications, such as phosphorylation, ubiquitylation, sumoylation, and neddylation, as well as by interaction with other proteins at the cell surface and in the cytoplasm. Activation of TGF-b receptors induces signaling via formation of Smad complexes that are translocated to the nucleus where they act as transcription factors, as well as via non-Smad pathways, including the Erk1/2, JNK and p38 MAP kinase pathways, and the Src tyrosine kinase, phosphatidylinositol 3 0 -kinase, and Rho GTPases.

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“…Another level of regulation may be provided by the interaction of the endoglin cytoplasmic domain with other cytosolic proteins as described in humans. This is the case of zyxin and zyxin-related protein 1 (ZRP-1) involved in actin organization and assembly around focal adhesions (Conley et al, 2004;Sanz-Rodriguez et al, 2004), Tctex2b, a member of the Tctex1/2 family of cytosolic dynein light chains, linking endoglin to the microtubule based transport machinery (Meng et al, 2006) or beta-arrestin2 involved in endoglin internalization in endocytic vesicles (Lee and Blobe, 2007). It will be interesting to investigate whether these mammalian endoglin binding proteins also have homologues that interact with chicken endoglin.…”

Section: Discussionmentioning

confidence: 99%

Characterization of chicken endoglin, a member of the zona pellucida family of proteins, and its tissue expression

Rossi

Langa

Gilsanz

et al. 2012

Gene

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Endoglin is a TGF- co-receptor expressed in endothelial cells, where it plays a crucial role in angiogenesis, cardiovascular development and vascular remodelling. In humans, mutations in the endoglin gene give rise to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disorder associated with vascular lesions in skin, mucosa and internal organs. So far, endoglin cDNA has been sequenced in several species from mammals, amphibians and birds. While in mammals the characterization of endoglin protein expression and function is well documented, little is known about the protein homologue in birds. In silico analysis by multiple sequences alignment showed a low homology score of 30-33 between the full length chicken endoglin protein and several mammalian homologues. However, a high homology score (80-85) was observed with the cytoplasmic and transmembrane regions and the overall structure of the zona pellucida (ZP) and orphan domains of the extracellular region appear to be conserved. Transient expression of chicken endoglin allowed the identification of a 180-kDa disulfide linked homodimer similar to the mammalian homologues. To further characterize its tissue expression, the novel specific monoclonal antibody (mAb) 7H5A8 was generated against chicken endoglin transfectant cells. The mAb 7H5A8 specifically recognized chicken endoglin by western blot, immunoprecipitation, immunofluorescence flow cytometry as well as immunofluorescence microscopy assays and displayed a positive staining of the endothelium in veins and arteries from frozen tissue sections of lung and bursa of Fabricius. These results may help to further understand the endoglin expression in vertebrates.

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Identification of Tctex2β, a Novel Dynein Light Chain Family Member That Interacts with Different Transforming Growth Factor-β Receptors

Cited by 41 publications

References 47 publications

Novel biochemical pathways of endoglin in vascular cell physiology

Novel biochemical pathways of endoglin in vascular cell physiology

Signaling Receptors for TGF-β Family Members

Characterization of chicken endoglin, a member of the zona pellucida family of proteins, and its tissue expression

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