High-level activation of cyclic AMP signaling attenuates bone morphogenetic protein 2-induced sympathoadrenal lineage

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Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation
07:00

Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation

Published on: August 23, 2018

Ming Ji1, Ourania M Andrisani

  • 1Department of Basic Medical Sciences, 625 Harrison Street, Purdue University, West Lafayette, IN 47907-2026, USA.

Molecular and Cellular Biology
|June 1, 2005
PubMed

Insights

High levels of cyclic AMP (cAMP) signaling suppress neural crest sympathoadrenal development while promoting melanogenesis. This dual role highlights how signal intensity dictates cell fate decisions.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • Neural crest (NC) cell specification relies on cyclic AMP (cAMP) signaling intensity.
  • High-level cAMP signaling suppresses sympathoadrenal lineage development through an unknown mechanism.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which high-level cAMP signaling influences neural crest cell differentiation.
  • To investigate the dual role of cAMP signaling in inhibiting sympathoadrenal development and inducing melanogenesis.

Main Methods:

  • Utilized neural crest cell cultures.
  • Investigated protein kinase A (PKA)-dependent signaling pathways including Rap1-B-Raf-ERK1/2.
  • Analyzed the impact on phospho-Smad1 accumulation and Mitf transcription.

Main Results:

  • High-level cAMP activates PKA, leading to Rap1-B-Raf-ERK1/2 signaling and cytoplasmic phospho-Smad1 accumulation.
  • This pathway terminates bone morphogenetic protein 2 (BMP2)-induced sympathoadrenal cell development.
  • cAMP signaling concurrently induces Mitf transcription and melanogenesis, dependent on CREB activation and PKA.

Conclusions:

  • High-level cAMP signaling plays a dual role in neural crest differentiation: inhibiting BMP2-induced sympathoadrenal development and promoting melanogenesis.
  • The intensity of signal transduction cascade activation is a critical determinant of cell lineage segregation.

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