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Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF-β signalling

  • Danielle KamatoEmail author
  • Bich Hang Do
  • Narin Osman
  • Benjamin P. Ross
  • Raafat Mohamed
  • Suowen Xu
  • Peter J. Little
Review
  • 76 Downloads

Abstract

Transforming growth factor (TGF)-β signalling pathways are intensively investigated because of their diverse association with physiological and pathophysiological states. Smad transcription factors are the key mediators of TGF-β signalling. Smads can be directly phosphorylated in the carboxy terminal by the TGF-β receptor or in the linker region via multiple intermediate serine/threonine kinases. Growth factors in addition to hormones and TGF-β can activate many of the same kinases which can phosphorylate the Smad linker region. Historically, Smad linker region phosphorylation was shown to prevent nuclear translocation of Smads and inhibit TGF-β signalling pathways; however, it was subsequently shown that Smad linker region phosphorylation can be a driver of gene expression. This review will cover the signalling pathways of Smad linker region phosphorylation that drive the expression of genes involved in pathology and pathophysiology. The role of Smad signalling in cell biology is expanding rapidly beyond its role in TGF-β signalling and many signalling paradigms need to be re-evaluated in terms of Smad involvement.

Keywords

Nuclear translocation G protein coupled receptors Serine/threonine kinase receptors Cancer Alk 5 Cell signalling 

Abbreviations

BMP

Bone morphogenetic proteins

C4ST-1

Chondroitin 4-O-sulfotransferase 1

CHSY1

Chondroitin synthase 1

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

GAG

Glycosaminoglycan

GPCR

G protein-coupled receptor

MMP

Matrix metalloproteinase

PAI-1

Plasminogen activator inhibitor-1

PAR

Protease-activated receptor

PDGF

Platelet-derived growth factor

PTKR

Protein tyrosine kinase receptor

S/TKR

Serine/threonine kinase receptor

TGFBR1

Transforming growth factor-β receptor type 1

TGF-β

Transforming growth factor-β

VSMCs

Vascular smooth muscle cells

Notes

Funding

DK was supported by the NHMRC (APP1160925) and National Heart Foundation Fellowship (102129). Support was received from the University of Queensland through a personal support package to PJL and by the University of Queensland Early Career Grant (DK) (Grant no. 1832825).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pharmacy Australia Centre of Excellence, School of PharmacyThe University of QueenslandWoolloongabbaAustralia
  2. 2.Department of PharmacyXinhua College of Sun Yat-Sen UniversityGuangzhouChina
  3. 3.Faculty of PharmacyTon Duc Thang UniversityHo Chi Minh CityVietnam
  4. 4.School of Medical SciencesRMIT UniversityBundooraAustralia
  5. 5.Department of ImmunologyMonash UniversityMelbourneAustralia
  6. 6.Department of Medicine, Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterUSA
  7. 7.Department of Basic Sciences, College of DentistryUniversity of MosulMosulIraq

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