Phosphorylation of threonine-2256 causes NG2 (green) to migrate from the cell's upper surface (above) to its front edge (below).
Even cancer cells have to slow down before they can divide, as do normal progenitor cells such as those that spawn oligodendrocytes in the brain. Evidence suggests that NG2, a proteoglycan in the cell membrane, enables cells to choose which action to perform. Cancer cells and progenitor cells manufacture NG2, for example, but most other cells don't.
Three years ago, the researchers showed that affixing a phosphate to a particular amino acid in NG2 changed cell behavior. Specifically, phosphorylating the threonine at position 2256 spurred cells to crawl. Makagiansar et al. wanted to discern what happens after phosphorylation of another threonine, found at position 2314.
This addition inhibited movement. The researchers also discovered that whereas phosphorylation of threonine-2256 checked cell proliferation, phosphorylation at the other position promoted it. The difference in function might stem from a shift in location.
Instead of signaling directly, NG2 relays its messages through β1 integrin. The team showed that, after phosphorylation of threonine-2256, NG2 and β1 integrin clustered at the front edge of the cell. But after phosphorylation of threonine-2314, NG2 and β1 integrin gathered in small spikes on the cell's upper surface. Overall, the results indicate that phosphorylation at each site triggers a contrasting response from the cell. If both sites were modified, threonine-2256 seemed to prevail, and the cell got going.
The researchers now hope to work out how phosphorylation at the two sites nudges NG2 into different locations. One possibility is that phosphorylation alters how NG2 interacts with scaffolding molecules such as MUPP1 and GRIP1 that control signaling interactions in the cytoplasm. 
