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 De Lorenzo, Sergei Kotenko, Raymond Birge

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Article number19
JournalCell Communication and Signaling
Volume14
Issue number1
DOIs
StatePublished - Sep 6 2016

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Epidermal Growth Factor
Protein-Tyrosine Kinases
Chemical activation
Phosphorylation
CHO Cells
Receptor Protein-Tyrosine Kinases
Transcriptome
Innate Immunity
Gene expression
Phosphors
Cell Movement
Screening
Carcinogenesis
Homeostasis
Cells
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Invasion
  • Metastasis
  • Signaling
  • TAM RTKs

Cite this

Kimani, Stanley G. ; Kumar, Sushil ; Davra, Viralkumar ; Chang, Yun Juan ; Kasikara, Canan ; Geng, Ke ; Tsou, Wen I. ; Wang, Shenyan ; Hoque, Mainul ; Boháč, Andrej ; Lewis-Antes, Anita ; De Lorenzo, Mariana ; Kotenko, Sergei ; Birge, Raymond. / Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase. In: Cell Communication and Signaling. 2016 ; Vol. 14, No. 1.
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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.",
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Kimani, SG, Kumar, S, Davra, V, Chang, YJ, Kasikara, C, Geng, K, Tsou, WI, Wang, S, Hoque, M, Boháč, A, Lewis-Antes, A, De Lorenzo, M, Kotenko, S & Birge, R 2016, 'Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase', Cell Communication and Signaling, vol. 14, no. 1, 19. https://doi.org/10.1186/s12964-016-0142-1

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase. / Kimani, Stanley G.; Kumar, Sushil; Davra, Viralkumar; Chang, Yun Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen I.; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana; Kotenko, Sergei; Birge, Raymond.

In: Cell Communication and Signaling, Vol. 14, No. 1, 19, 06.09.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase

AU - Kimani, Stanley G.

AU - Kumar, Sushil

AU - Davra, Viralkumar

AU - Chang, Yun Juan

AU - Kasikara, Canan

AU - Geng, Ke

AU - Tsou, Wen I.

AU - Wang, Shenyan

AU - Hoque, Mainul

AU - Boháč, Andrej

AU - Lewis-Antes, Anita

AU - De Lorenzo, Mariana

AU - Kotenko, Sergei

AU - Birge, Raymond

PY - 2016/9/6

Y1 - 2016/9/6

N2 - 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.

AB - 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.

KW - Invasion

KW - Metastasis

KW - Signaling

KW - TAM RTKs

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U2 - 10.1186/s12964-016-0142-1

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