Differential phosphorylation of NG2 proteoglycan by ERK and PKCα helps balance cell proliferation and migration

Two distinct Thr phosphorylation events within the cytoplasmic domain of the NG2 proteoglycan help regulate the cellular balance between proliferation and motility. Protein kinase C alpha mediates the phosphorylation of NG2 at Thr(2256), resulting in enhanced cell motility. Extracellular signal-regulated kinase phosphorylates NG2 at Thr(2314), stimulating cell proliferation. The effects of NG2 phosphorylation on proliferation and motility are dependent on beta 1-integrin activation. Differential cell surface localization of the two distinctly phosphorylated forms of NG2 may be the mechanism by which the l beta 1-integrin interaction promotes proliferation in one case and motility in the other. NG2 phosphorylated at Thr(2314) colocalizes with beta 1-integrin on microprotrusions from the apical cell surface. In contrast, NG2 phosphorylated at Thr(2256) colocalizes with beta 1-Integrin on lamellipodia at the leading edges of cells. Thus, phosphorylation and the resulting site of NG2-integrin localization may determine the specific downstream effects of integrin signaling.