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

Stanley G Kimani; Sushil Kumar; Viralkumar Davra; Yun-Juan Chang; Canan Kasikara; Ke Geng; Wen-I Tsou; Shenyan Wang; Mainul Hoque; Andrej Boháč; Anita Lewis-Antes; Mariana S De Lorenzo; Sergei V Kotenko; Raymond B Birge

doi:10.1186/s12964-016-0142-1

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

Journal article

Open access

Peer reviewed

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

Stanley G Kimani, Sushil Kumar, Viralkumar Davra, Yun-Juan Chang, Canan Kasikara, Ke Geng, Wen-I Tsou, Shenyan Wang, Mainul Hoque, Andrej Boháč, …

Cell communication and signaling, Vol.14(1), pp.19-19

09/06/2016

DOI: https://doi.org/10.1186/s12964-016-0142-1

PMCID: PMC5011882

PMID: 27595981

Abstract

Animals

c-Mer Tyrosine Kinase

Cell Movement

CHO Cells

Cricetinae

Cricetulus

Female

Humans

Mammary Neoplasms, Experimental - metabolism

Mammary Neoplasms, Experimental - pathology

Mice

Mice, Inbred BALB C

Proto-Oncogene Proteins - genetics

Proto-Oncogene Proteins - metabolism

Receptor Protein-Tyrosine Kinases - genetics

Receptor Protein-Tyrosine Kinases - metabolism

Receptor, Epidermal Growth Factor - genetics

Receptor, Epidermal Growth Factor - metabolism

Signal Transduction

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

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Title: Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase
Creators: Stanley G Kimani - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Sushil Kumar - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Viralkumar Davra - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Yun-Juan Chang - Rutgers, Biomedical and Health Sciences, OIT/High Performance and Research Computing, 185 South Orange Ave, Newark, NJ, 07103, USA
Canan Kasikara - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Ke Geng - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Wen-I Tsou - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Shenyan Wang - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Mainul Hoque - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Genomics Research Program, Rutgers- New Jersey Medical School, 185 South Orange Ave, Newark, NJ, 07103, USA
Andrej Boháč - Biomagi, Ltd, Mamateyova 26, 851 04, Bratislava, Slovakia
Anita Lewis-Antes - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Mariana S De Lorenzo - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Sergei V Kotenko - Rutgers, Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers- New Jersey Medical School, 205 South Orange Ave, Newark, NJ, 07103, USA
Raymond B Birge - 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
Publication Details: Cell communication and signaling, Vol.14(1), pp.19-19
Date published: 09/06/2016
Grant note: R01 CA165077 / NCI NIH HHS R01 AI104669 / NIAID NIH HHS S10 OD018206 / NIH HHS
Academic Unit: Cell Biology and Molecular Medicine (NJMS); Biochemistry (NJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665888904646