Research ArticleCell Biology

Context-specific flow through the MEK/ERK module produces cell- and ligand-specific patterns of ERK single and double phosphorylation

See allHide authors and affiliations

Science Signaling  02 Feb 2016:
Vol. 9, Issue 413, pp. ra13
DOI: 10.1126/scisignal.aab1967

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

ERK phosphorylation patterns

In the ERK pathway, the dual-specificity kinase MEK phosphorylates a threonine and a tyrosine residue in ERK, and this dual-phosphorylated form is the fully active kinase. Iwamoto et al. used mass spectrometry, quantitative Western blotting, and mathematical modeling to explore MEK-dependent phosphorylation dynamics of ERK in skin and liver cells exposed to either a cytokine, IL-6, or a growth factor, HGF. Not surprisingly, the different stimuli produced different dynamics of ERK phosphorylation, and skin and liver cells responded differently to the same ligand. The dynamics of the changes in the abundance of the phosphorylated forms of ERK (pT-ERK, pY-ERK, and pTpY-ERK) and the relative distributions of the single- and double-phosphorylated forms of ERK were different. Mathematical modeling indicated that distinct network structures with or without regulated feedback loops produced the different dynamics of ERK phosphorylation and distributions of phosphorylated ERK. This study provides biochemical insight into how a single pathway can produce distinct responses, such as differentiation or proliferation.

View Full Text