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Cell Commun Signal. 2016 Sep 6;14(1):19. doi: 10.1186/s12964-016-0142-1.

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

Author information

1
Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA.
2
Rutgers, Biomedical and Health Sciences, OIT/High Performance and Research Computing, 185 South Orange Ave, Newark, NJ, 07103, USA.
3
Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Genomics Research Program, Rutgers- New Jersey Medical School, 185 South Orange Ave, Newark, NJ, 07103, USA.
4
Department of Organic Chemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynská dolina, Ilkovičova 6, 842 15, Bratislava, Slovakia.
5
Biomagi, Ltd, Mamateyova 26, 851 04, Bratislava, Slovakia.
6
Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA. birgera@njms.rutgers.edu.

Abstract

BACKGROUND:

Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis.

METHODS:

In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling.

RESULTS:

Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk.

CONCLUSION:

These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

KEYWORDS:

Invasion; Metastasis; Signaling; TAM RTKs

PMID:
27595981
PMCID:
PMC5011882
DOI:
10.1186/s12964-016-0142-1
[Indexed for MEDLINE]
Free PMC Article

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