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A network map of thrombopoietin signaling

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Journal of Cell Communication and Signaling Aims and scope

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.

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Abbreviations

THPO:

Thrombopoietin

MPL:

MPL proto-oncogene, thrombopoietin receptor

JAK2:

Janus kinase 2

STAT:

Signal transducer and activator of transcription protein

MAPK:

Mitogen-activated protein kinase

PIK3:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

MPN:

Myeloproliferative neoplasms

RT-PCR:

Real-time polymerase chain reaction

BioPAX:

Biological Pathway Exchange

SBML:

Systems Biology Markup Language

PSI-MI:

Proteomics Standards Initiative for Molecular Interaction`

PTM:

Post-translational modification

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Acknowledgements

We thank the Department of Biotechnology, Government of India for research support to Institute of Bioinformatics. FAB is a recipient of a Senior Research Fellowship from University Grants Commission (UGC), JA is a recipient of Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India.

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  1. Firdous A. Bhat and Jayshree Advani contributed equally to this work.

Authors and Affiliations

  1. Institute of Bioinformatics, International Technology Park, Bangalore, 560 066, India

    Firdous A. Bhat, Jayshree Advani, Aafaque Ahmad Khan, Sonali Mohan, Harsha Gowda, T. S. Keshava Prasad & Aditi Chatterjee

  2. School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690525, India

    Firdous A. Bhat

  3. Manipal Academy of Higher Education, Manipal, 576104, India

    Jayshree Advani

  4. School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India

    Aafaque Ahmad Khan

  5. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Arnab Pal

  6. Department of Haematology, Nil Ratan Sircar Medical College and Hospital, Kolkata, 700014, India

    Prantar Chakrabarti

  7. Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), University Road, Mangalore, 575018, India

    T. S. Keshava Prasad

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  1. Firdous A. Bhat
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Correspondence to T. S. Keshava Prasad or Aditi Chatterjee.

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Bhat, F.A., Advani, J., Khan, A.A. et al. A network map of thrombopoietin signaling. J. Cell Commun. Signal. 12, 737–743 (2018). https://doi.org/10.1007/s12079-018-0480-4

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