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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Casein kinase 1 regulates Sprouty2 in FGF-ERK signaling

D G R Yim1, S Ghosh2, G R Guy3

  • 11] Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore [2] Signal Transduction Laboratory, Institute for Molecular and Cellular Biology, Biopolis, Singapore [3] Genome Institute of Singapore, Biopolis, Singapore.

Oncogene
|January 29, 2014
PubMed

Insights

Casein kinase 1 (CK1) phosphorylates Sprouty2 (SPRY2), a tumor suppressor. CK1 activity is essential for SPRY2

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • Sprouty2 (SPRY2) acts as a tumor suppressor by negatively regulating receptor tyrosine kinase signaling pathways.
  • SPRY2 inhibits fibroblast growth factor receptor (FGFR) signaling by interfering with the GRB2-SOS complex, which is crucial for RAS-ERK pathway activation.
  • The phosphorylation of SPRY2 by kinases modulates its interaction with GRB2, but the specific kinases involved remain unidentified.

Purpose of the Study:

  • To investigate the role of Casein Kinase 1 (CK1) in the phosphorylation and function of Sprouty2 (SPRY2).
  • To determine if CK1 activity is required for SPRY2's inhibitory effects on FGF-RAS-ERK signaling and FGF-stimulated cellular processes.

Main Methods:

  • Assessed the effect of CK1 inhibition and disruption of CK1-SPRY2 binding on SPRY2's ability to inhibit FGF-ERK signaling.
  • Examined the impact of CK1 activity on SPRY2's interaction with GRB2.
  • Evaluated the necessity of CK1 activity for SPRY2's inhibition of FGF-stimulated neurite outgrowth in PC12 cells.
  • Correlated CSNK1E transcript levels with FGF1/FGF7 expression in human gastric cancer samples.

Main Results:

  • Inhibition of CK1 activity or disruption of CK1 binding to SPRY2 abrogated SPRY2's inhibitory effect on FGF-ERK signaling.
  • CK1 activity was found to be necessary for SPRY2's interaction with GRB2.
  • CK1 activity and binding are critical for SPRY2 to inhibit FGF-stimulated neurite outgrowth in PC12 cells.
  • CSNK1E transcript abundance showed a negative correlation with FGF1/FGF7 message in gastric cancer, supporting SPRY2's inhibitory role.

Conclusions:

  • CK1 is a key kinase that phosphorylates SPRY2, regulating its function as a negative modulator of FGF signaling.
  • CK1 activity is essential for SPRY2's tumor suppressor function by maintaining its inhibitory interaction with GRB2.
  • Targeting CK1 activity may offer a therapeutic strategy for FGF/SPRY2-related diseases, including certain cancers.

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