Phospho-MEK1 (Thr292) Antibody #51265

MEK1 and MEK2, also called MAPK or Erk kinases, are dual-specificity protein kinases that function in a mitogen activated protein kinase cascade controlling cell growth and differentiation (1-3). Activation of MEK1 and MEK2 occurs through phosphorylation of two serine residues at positions 217 and 221, located in the activation loop of subdomain VIII, by Raf-like molecules. MEK1/2 is activated by a wide variety of growth factors and cytokines and also by membrane depolarization and calcium influx (1-4). Constitutively active forms of MEK1/2 are sufficient for the transformation of NIH/3T3 cells or the differentiation of PC-12 cells (4). MEK activates p44 and p42 MAP kinase by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.
In response to integrin signaling, p21-activated kinase -1 (PAK-1) phosphorylates MEK1 at Ser298, which enhances MEK1-ERK2 complex formation and MEK1 activation by Raf-1. These events positively regulate the Raf-1-MEK-ERK signaling cascade (5-9). Research studies have identified a negative regulatory loop in the Raf-1-MEK-ERK signaling cascade, in which ERK2-dependent phosphorylation of MEK1 at Thr292 negatively regulates MEK1 activation following cell adhesion. Specifically, ERK2-dependent phosphorylation of MEK1 also attenuates its PAK-1-mediated phosphorylation, contributing to a reduction in Raf-dependent phosphorylation of residues within the MEK1 activation loop (7,10).