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The ROS1 Receptor Family

  • Chapter
Receptor Tyrosine Kinases: Family and Subfamilies

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Abstract

The proto-oncogene receptor tyrosine kinase ROS1 is an evolutionarily conserved receptor that functions in development and cancer. Using genetic models and biochemical approaches, ROS1 was shown to play distinctive roles in epithelial cell differentiation during the development of a variety of organs. Although substantial, these advances remain hampered by the absence of an identified ligand, making ROS1 one of the last two remaining orphan receptor tyrosine kinases. Recent global in-depth cancer genomic studies have unveiled a variety of different chromosomal rearrangements that leads to the oncogenic activation of ROS1. Studies on the resulting ROS1 fusion kinases have shed light on the molecular mechanisms underlying ROS1 transforming activities. ROS1 and its oncogenic fusion variants therefore constitute clinically relevant targets for cancer therapeutic intervention. This chapter highlights the various roles that this receptor plays in multiple system networks in normalcy and disease and points to future directions towards the elucidation of ROS1 function in the context of ligand identification, signaling pathways and clinical applications.

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Author information

Authors and Affiliations

  1. Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington St., 5609, Boston, MA, 02111, USA

    Alain Charest M.Sc., Ph.D.

  2. Department of Neurosurgery, Tufts Medical Center, Boston, MA, USA

    Alain Charest M.Sc., Ph.D.

  3. Programs in Genetics and Neuroscience, Tufts University School of Medicine, Boston, MA, USA

    Alain Charest M.Sc., Ph.D.

Authors
  1. Alain Charest M.Sc., Ph.D.
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Corresponding author

Correspondence to Alain Charest M.Sc., Ph.D. .

Editor information

Editors and Affiliations

  1. School of Medicine and Public Health Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA

    Deric L. Wheeler

  2. Department of Biological Regulation, Rehovot, Israel

    Yosef Yarden

Receptor at a glance: ROSss1

Receptor at a glance: ROSss1

Chromosome location

6q22

Gene size (bp)

137,489 bp

Intron/exon numbers

44 exons

mRNA size (5′, ORF, 3′)

7,375 nt

Amino acid number

2,347 amino acids

kDa

~260 kD

Posttranslational modifications

30 potential N-linked (GlcNAc), Phosphorylation

Domains

9 FN-III, 3 YWTD modules, extracellular, transmembrane domain, kinase domain

Ligands

Unknown

Known dimerizing partners

N/A

Pathways activated

RAS/MEK/ERK, STAT3, PI3K-AKT-mTOR, VAV3, SHP-1/2

Tissues expressed

Mostly in lungs

Human diseases

Cancer, heart

Knockout mouse phenotype

Male sterility, lack of epididymal function

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© 2015 Springer International Publishing Switzerland

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Cite this chapter

Charest, A. (2015). The ROS1 Receptor Family. In: Wheeler, D., Yarden, Y. (eds) Receptor Tyrosine Kinases: Family and Subfamilies. Springer, Cham. https://doi.org/10.1007/978-3-319-11888-8_14

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