Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) reprograms growth factor signaling by inhibiting threonine phosphorylation of fibroblast receptor substrate 2alpha.

ABSTRACT: Changes in cellular expression of phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) are linked to insulin resistance, tumor cell invasion, and cellular senescence; these changes alter the activation of the extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway. Here, we define the mechanism whereby increased PEA-15 expression promotes and sustains ERK1/2 activation. PEA-15 binding prevented ERK1/2 membrane recruitment and threonine phosphorylation of fibroblast receptor substrate 2alpha (FRS2alpha), a key link in fibroblast growth factor (FGF) receptor activation of ERK1/2. This reduced threonine phosphorylation led to increased FGF-induced tyrosine phosphorylation of FRS2alpha, thereby enhancing downstream signaling. Conversely, short hairpin

SUBMITTER: Haling JR 

PROVIDER: S-EPMC2820429 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature