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Tyro‐3, Axl and Mer Chimeric reporter systems shows the differential regulations of the TAM family receptor tyrosine kinases
Author(s) -
Kimani Stanley Gititu,
Kumar Sushil,
Kotenko Sergei,
Birge Raymond
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1117.1
Subject(s) - receptor tyrosine kinase , gas6 , microbiology and biotechnology , receptor , biology , axl receptor tyrosine kinase , signal transduction , receptor protein tyrosine kinases , cancer research , kinase , cell signaling , tyrosine kinase , extracellular , jak stat signaling pathway , biochemistry
T yro‐3, A xl and M er (TAMs) are a family of receptor tyrosine kinases that mediate diverse cellular functions including clearance of apoptotic cells and dampening of inflammatory responses by suppressing the activation of macrophages, dendritic cells, and NK cells. Additionally, TAMs are implicated in a number of human malignancies, where the level of expression is often associated with more aggressive staging of the cancers and poor prognosis. Although the activation of TAMs leads to downstream signaling through various known pathways, the exact mechanism within each cellular context remains to be completely elucidated. To study specific post‐receptor mechanisms of signaling of individual TAM, EGFR/TAM chimeric receptors were created by fusing the extracellular domains human EGFR in frame with the trans‐membrane and intracellular domains of each human TAM receptor and stable lines were generated in hamster CHO cell. We report that TAMs have unique post‐receptor activation signatures as demonstrated by RNA‐seq, Kinomeview profiling, and xCELLigence‐based biological experiments. Together, these data show that TAM receptors exhibit unique post‐receptor signaling signatures in gene expression leading to non‐overlapping biological outcomes. Support or Funding Information New Jersey Commission on Cancer Research (NJCCR) Postdoctoral Fellowship to study “Epithelial efferocytosis as a tumor immune escape mechanism in breast cancer”‐Stanley Kimani(A) Wildtype TAM receptors contain an extracellular, transmembrane and intracellular kinase domain. The ligands, (Gas6 and Protein S) serve as bridging molecules to link TAMs on phagocytic cell to externalized PS on apoptotic cells (B) EGFR/TAM chimeric receptors created by fusing the extracellular domains human EGFR with the trans‐membrane and intracellular domains of each TAM receptor.