Constitutive phosphorylation of a Rac GAP MgcRacGAP is implicated in v-Src-induced transformation of NIH3T3 cells
2009
MgcRacGAP plays critical roles in cell division through regulating
Rho family
small GTPases. As we previously reported,
phosphorylationof MgcRacGAP on serine 387 (S387) is induced by
Aurora B kinaseat the
midbodyduring
cytokinesis, which is a critical step of
cytokinesis.
Phosphorylationof S387-MgcRacGAP converts it from RacGAP to RhoGAP, leading to completion of
cytokinesis. Here we show that MgcRacGAP is prominently
phosphorylatedon S387 even in the
interphaseof
v-Src-transformed NIH3T3 cells in the cytoplasm, but not in the
interphaseof parental NIH3T3 or H-RasV12-transformed NIH3T3 cells. Interestingly, levels of
phosphorylationon S387 (pS387) correlated with soft agar colony-forming abilities of
v-Src-transformed NIH3T3 cells. Expression of a
phosphorylation-mimic mutant MgcRacGAP-S387D enhanced colony formation of
v-Src-transformed NIH3T3 cells. Surprisingly, a
Rac1inhibitor but not kinase inhibitors including
Aurora B kinaseinhibitor specifically inhibited
phosphorylationof S387-MgcRacGAP in
v-Src-transformed NIH3T3 cells, suggesting the
v-Src-induced pathological positive feedback mechanisms towards
Rac1activation using pS387-MgcRacGAP. These results indicated the difference in the mechanisms between
v-Src- and H-RasV12-induced transformation, and should shed some light on pathological roles of disordered
phosphorylationof MgcRacGAP at S387 in
v-Src-induced cell transformation. (Cancer Sci 2009; 100: 1675–1679)
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