TITLE

TGF-β Prodomain Alignments Reveal Unexpected Cysteine Conservation Consistent with Phylogenetic Predictions of Cross-Subfamily Heterodimerization

AUTHOR(S)
Wisotzkey, Robert G.; Newfeld, Stuart J.
PUB. DATE
February 2020
SOURCE
Genetics;Feb2020, Vol. 214 Issue 2, p447
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Evolutionary relationships between prodomains in the TGF-b family have gone unanalyzed due to a perceived lack of conservation. We developed a novel approach, identified these relationships, and suggest hypotheses for new regulatory mechanisms in TGF-b signaling. First, a quantitative analysis placed each family member from flies, mice, and nematodes into the Activin, BMP, or TGF-b subfamily. Second, we defined the prodomain and ligand via the consensus cleavage site. Third, we generated alignments and trees from the prodomain, ligand, and full-length sequences independently for each subfamily. Prodomain alignments revealed that six structural features of 17 are well conserved: three in the straitjacket and three in the arm. Alignments also revealed unexpected cysteine conservation in the "LTBP-Association region" upstream of the straitjacket and in b8 of the bowtie in 14 proteins from all three subfamilies. In prodomain trees, eight clusters across all three subfamilies were present that were not seen in the ligand or fulllength trees, suggesting prodomain-mediated cross-subfamily heterodimerization. Consistency between cysteine conservation and prodomain clustering provides support for heterodimerization predictions. Overall, our analysis suggests that cross-subfamily interactions are more common than currently appreciated and our predictions generate numerous testable hypotheses about TGF-b function and evolution.
ACCESSION #
141655358

 

Related Articles

  • Ancient and diverged TGF-β signaling components in Nasonia vitripennis. Özüak, Orhan; Buchta, Thomas; Roth, Siegfried; Lynch, Jeremy // Development Genes & Evolution;Dec2014, Vol. 224 Issue 4-6, p223 

    The transforming growth factor beta (TGF)-β signaling pathway and its modulators are involved in many aspects of cellular growth and differentiation in all metazoa. Although most of the core components of the pathway are highly conserved, many lineage-specific adaptations have been observed...

  • Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice. Zhou, Wei; Yu, Lipeng; Fan, Jin; Wan, Bowen; Jiang, Tao; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Hu, Zhaoxing // Cellular Physiology & Biochemistry (Karger AG);Jul2017, Vol. 42 Issue 2, p551 

    Background/Aims: Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-β (TGF-β) signaling pathway. Methods:...

  • Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β. Abreu, José G.; Ketpura, Nan I.; Reversade, Bruno; De Robertis, E. M. // Nature Cell Biology;Aug2002, Vol. 4 Issue 8, p599 

    Connective-tissue growth factor (CTGF) is a secreted protein implicated in multiple cellular events including angiogenesis, skeletogenesis and wound healing. It is a member of the CCN family of secreted proteins, named after CTGF, cysteine-rich 61 (CYR61), and nephroblastoma overexpressed (NOV)...

  • BMP-7 and Proximal Tubule Epithelial Cells: Activation of Multiple Signaling Pathways Reveals a Novel Anti-fibrotic Mechanism. Reza Motazed; Paul Colville-Nash; Jonathan Kwan; Mark Dockrell // Pharmaceutical Research;Oct2008, Vol. 25 Issue 10, p2440 

    Abstract Purpose  Bone morphogenic protein-7 (BMP-7) is a member of the transforming growth factor β (TGFβ) superfamily involved in organogenesis. Recent work suggests that BMP-7 can reverse the fibrotic effects of TGFβ but the underlying mechanism is unknown. We sought to...

  • Intimate Relationship Between TGF-β/BMP Signaling and Runt Domain Transcription Factor, PEBP2/CBF. Suk-Chul Bae; Kycong-Sook Lee; Yu-Wen Zhang; Ito, Yoshiaki // Journal of Bone & Joint Surgery, American Volume;Mar2001 Supplement 1 Part 1, Vol. 83-A, pS1-48 

    Background: When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factorβ1 (TGF-β1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein-2 (BMP-2) not only blocks myogenic differentiation but also induces...

  • Enamel Matrix Derivative Gel Stimulates Signal Transduction of BMP and TGF-β. Suzuki, S.; Nagano, T.; Yamakoshi, Y.; Gomi, K.; Arai, T.; Fukae, M.; Katagiri, T.; Oida, S. // Journal of Dental Research;Jun2005, Vol. 84 Issue 6, p510 

    It has been shown that Emdogain® Gel (Emd-Gel) containing enamel matrix proteins promotes biomineralization, such as osteogenesis and cementogenesis, during the regeneration of periodontal tissues. However, the growth factors involved in these activities of Emd-Gel remain unclear. In this...

  • The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis. Martínez, Víctor G.; Sacedón, Rosa; Hidalgo, Laura; Valencia, Jaris; Fernández-Sevilla, Lidia M.; Hernández-López, Carmen; Vicente, Angeles; Varas, Alberto // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    Bone Morphogenetic Proteins (BMPs) form a group of secreted factors that belongs to the TGF-β superfamily. Among different roles in a number of immune cell types, BMPs are known to regulate T cell development within the thymus, although the role of BMP signaling in human mature T cells...

  • The differential pathways of bone morphogenetic protein (BMP)-4 and -7 in the suppression of the bovine granulosa cell apoptosis. Takefumi Kayamori; Naomichi Kosaka; Akio Miyamoto; Takashi Shimizu // Molecular & Cellular Biochemistry;Mar2009, Vol. 323 Issue 1/2, p161 

    Abstract  Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-beta family, are crucial factors in follicular growth and development in the mammalian ovary. In this study, we examined the effects of BMP-4 and BMP-7 on granulosa cell apoptosis. Here, we report...

  • Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning. Luong, Hien T. T; Chaplin, Justin; McRae, Allan F; Medland, Sarah E; Willemsen, Gonneke; Nyholt, Dale R; Henders, Anjali K; Hoekstra, Chantal; Duffy, David L; Martin, Nicholas G; Boomsma, Dorret I; Montgomery, Grant W; Painter, Jodie N // Twin Research & Human Genetics;Oct2011, Vol. 14 Issue 5, p408 

    Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics