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J Cell Commun Signal. 2018 Dec;12(4):737-743. doi: 10.1007/s12079-018-0480-4. Epub 2018 Jul 24.

A network map of thrombopoietin signaling.

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore, 560 066, India.
2
School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India.
3
Manipal Academy of Higher Education, Manipal, 576104, India.
4
School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
5
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
6
Department of Haematology, Nil Ratan Sircar Medical College and Hospital, Kolkata, 700014, India.
7
Institute of Bioinformatics, International Technology Park, Bangalore, 560 066, India. keshav@yenepoya.edu.in.
8
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), University Road, Mangalore, 575018, India. keshav@yenepoya.edu.in.
9
Institute of Bioinformatics, International Technology Park, Bangalore, 560 066, India. aditi@ibioinformatics.org.

Abstract

Thrombopoietin (THPO), also known as megakaryocyte growth and development factor (MGDF), is a cytokine involved in the production of platelets. THPO is a glycoprotein produced by liver and kidney. It regulates the production of platelets by stimulating the differentiation and maturation of megakaryocyte progenitors. It acts as a ligand for MPL receptor, a member of the hematopoietic cytokine receptor superfamily and is essential for megakaryocyte maturation. THPO binding induces homodimerization of the receptor which results in activation of JAKSTAT and MAPK signaling cascades that subsequently control cellular proliferation, differentiation and other signaling events. Despite the importance of THPO signaling in various diseases and biological processes, a detailed signaling network of THPO is not available in any publicly available database. Therefore, in this study, we present a resource of signaling events induced by THPO that was manually curated from published literature on THPO. Our manual curation of thrombopoietin pathway resulted in identification of 48 molecular associations, 66 catalytic reactions, 100 gene regulation events, 19 protein translocation events and 43 activation/inhibition reactions that occur upon activation of thrombopoietin receptor by THPO. THPO signaling pathway is made available on NetPath, a freely available human signaling pathway resource developed previously by our group. We believe this resource will provide a platform for scientific community to accelerate further research in this area on potential therapeutic interventions.

KEYWORDS:

BioPAX; Cancer; Hematopoiesis; Thrombocytopenia; Thrombocytosis

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