Mammalian neutrophils and the amoebalike cells of the slime mold Dictyostelium discoideum respond to chemoattractants by engaging specific signaling mechanisms at the front and rear ends of the cell. During chemotaxis, two members of the Rho family of small GTPases, Rac and Cdc42, control actin dynamics at the leading edge of the cell. Meanwhile, RhoA controls contraction at the trailing end, which is where the phosphatase PTEN resides (which has the effect of restricting its phosphatidylinositol trisphosphate substrate to the front end).
Li et al. discovered that treatment of neutrophils or human embryonic kidney (HEK) cells with an inhibitor of RhoA-associated kinase (ROCK) blocked PTEN localization in response to a chemo-attractant. Further analysis of HEK cells revealed that PTEN translocation and activation could be induced by a constitutively activated form of RhoA and also by active Cdc42. A mutant PTEN that lacked four putative phosphorylation sites failed to rescue the chemotactic defects of cells lacking PTEN, and the mutant form also lacked lipid phosphatase activity when expressed with constitutively activated RhoA, suggesting that a RhoA-ROCK signaling pathway is required for phosphorylating and activating PTEN. Because neutrophils that were unable to activate Cdc42 in response to a chemoattractant also failed to localize RhoA and PTEN to the cell posterior, these two GTPase signaling pathways may cooperate to control PTEN during chemotaxis. — LDC
Nat. Cell Biol. 10.1038/ncb1236 (2005).