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Down-regulation of ERK1 and ERK2 activity during differentiation of the intestinal cell line HT-29

Diomira Luongo1, Giuseppe Mazzarella, Ragione Fulvio Della

  • 1Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy.

Molecular and Cellular Biochemistry
|April 16, 2002
PubMed

Insights

Mitogen-activated protein kinases (MAPKs) like ERK 1 and ERK 2 are crucial for intestinal cell development. Their regulation changes significantly during differentiation, impacting intestinal cell proliferation and function.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Biology

Background:

  • Signal transduction pathways governing intestinal epithelial cell proliferation and differentiation are not fully understood.
  • Mitogen-activated protein kinases (MAPKs) are increasingly recognized for their critical roles in normal intestinal development.

Purpose of the Study:

  • To investigate the regulation of ERK 1 (p44) and ERK 2 (p42) activity and phosphorylation during HT-29 intestinal cell differentiation.
  • To elucidate the role of MAP kinases in intestinal cell proliferation and differentiation.

Main Methods:

  • Utilized the HT-29 intestinal cell line.
  • Assessed ERK 1 and ERK 2 activity and phosphorylation levels under different differentiation conditions (fetal calf serum, butyrate, glucose-free medium).
  • Monitored nuclear translocation of ERK 1 and ERK 2.

Main Results:

  • Fetal calf serum induced rapid ERK phosphorylation and kinase activity increase, with concurrent nuclear translocation, indicating classical regulation in proliferating cells.
  • Butyrate-induced differentiation selectively down-regulated ERK 2 activity and phosphorylation without affecting ERK 1.
  • Differentiation in glucose-free medium led to progressive ERK 1 and ERK 2 dephosphorylation and inactivation, rendering the MAP kinase pathway unresponsive to serum stimulation.

Conclusions:

  • ERK 1 and ERK 2 regulation undergoes significant alterations during intestinal cell differentiation.
  • These changes result in an altered responsiveness of the MAP kinase pathway during intestinal cell differentiation, impacting cellular processes.

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