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A network map of netrin receptor UNC5B-mediated signaling

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Journal of Cell Communication and Signaling Aims and scope

Abstract

UNC-5 Homolog B (UNC5B) is a member of the dependence receptor family. This family of receptors can induce two opposite intracellular signaling cascades depending on the presence or absence of the ligand and is thus capable of driving two opposing processes. UNC5B signaling has been implicated in several cancers, where it induces cell death in the absence of its ligand Netrin-1 and promotes cell survival in its presence. In addition, inhibition of Netrin-1 ligand has been reported to decrease invasiveness and angiogenesis in tumors. UNC5B signaling pathway has also been reported to be involved in several processes such as neural development, developmental angiogenesis and inflammatory processes. However, literature pertaining to UNC5B signaling is scarce and scattered. Considering the importance of UNC5B signaling, we developed a resource of signaling events mediated by UNC5B. Using data mined from published literature, we compiled an integrated pathway map consisting of 88 UNC5B-mediated signaling events and 55 proteins. These signaling events include 27 protein-protein interaction events, 33 catalytic events involving various post-translational modifications, 9 events of UNC5B-mediated protein activation/inhibition, 27 gene regulation events and 2 events of translocation. This pathway resource has been made available to the research community through NetPath (http://www.netpath.org/), a manually curated resource of signaling pathways (Database URL: http://www.netpath.org/pathways?path_id=NetPath_172). The current resource provides a foundation for the understanding of UNC5B-mediated cellular responses. The development of resource will serve researchers to explore the mechanisms of UNC-5B signaling in cancers.

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Abbreviations

UNC5B:

UNC5 netrin receptor B

PP2A:

Protein Phosphate 2A

NTN1:

Netrin-1

TS:

Thrombospondin domain

DCC:

Deleted in colorectal cancer

DAPK:

Death-associated protein kinase

IG:

Immunoglobulin Domain

DD:

Death Domain

PPI:

Protein-protein interaction

PTM:

Post-translational modification

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Acknowledgments

The work was supported by DST INSPIRE fellowship to Sameer Ahmed Bhat. We also thank Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka for the support to the Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University) under the Biotechnology Skill Enhancement Programme (BiSEP) in Multiomics Technology. We also thank the Department of Biotechnology, Government of India, for giving support to Dr. Shaida Andrabi through Ramalingaswami Fellowship.

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Authors and Affiliations

  1. Department of Biotechnology, University of Kashmir, Srinagar, 190006, India

    Sameer Ahmed Bhat & Khalid Majid Fazili

  2. Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, 575 018, India

    Sumrati Gurtoo, Sayali Chandrashekhar Deolankar, T. S. Keshava Prasad & Yashwanth Subbannayya

  3. Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India

    Jayshree Advani & T. S. Keshava Prasad

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

    Jayshree Advani

  5. Department of Surgical Oncology. Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore, 575 018, India

    Rohan Shetty

  6. Department of Biochemistry, University of Kashmir, Srinagar, 190006, India

    Shaida Andrabi

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  1. Sameer Ahmed Bhat
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  2. Sumrati Gurtoo
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  3. Sayali Chandrashekhar Deolankar
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  4. Khalid Majid Fazili
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  5. Jayshree Advani
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  6. Rohan Shetty
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  7. T. S. Keshava Prasad
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  8. Shaida Andrabi
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  9. Yashwanth Subbannayya
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Correspondence to Shaida Andrabi or Yashwanth Subbannayya.

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Bhat, S.A., Gurtoo, S., Deolankar, S.C. et al. A network map of netrin receptor UNC5B-mediated signaling. J. Cell Commun. Signal. 13, 121–127 (2019). https://doi.org/10.1007/s12079-018-0485-z

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