PRL XXXX phosphatases regulate rho family GTPases to promote invasion and motility.

@entity33760 @entity63312 @entity5 @entity3547 @entity5605 @entity71967 @entity15931 @entity43545 @entity71966 @entity14 @entity3 @entity669
@entity63312 , @entity43545 , and @entity15931 [also known as @entity63312 , @entity43545 , and @entity15931 , respectively] constitute a unique family of putative protein @entity669 phosphatases (PTPs) modified by farnesylation. @entity15931 is amplified and its message is up-regulated in @entity14 metastases. Its ectopic expression promotes invasive and metastatic properties, supporting a causal link between @entity15931 and late-stage @entity5 development. However, neither PRL phosphatase substrates nor their signaling pathways have been defined. To address possible mechanisms for the biological activity of @entity15931 , we sought to identify its downstream targets, reasoning that regulators of motility and invasion, such as the Rho family of small GTPases, might be logical candidates. We found that levels of active @entity3547 and @entity33760 were increased 4- to 7-fold in SW480 @entity14 cells expressing exogenous @entity63312 and @entity15931 , and that PRL-mediated motility and Matrigel invasion were blocked by pharmacologic inhibition of Rho kinase (ROCK), a key Rho effector. In contrast, the activity of Rac was reduced by PRL PTPs, whereas @entity5605 activity was unaffected. @entity15931 stimulated transcription driven by the serum response element in a Rho-dependent manner. We also confirmed that the ability of PRL PTPs to induce invasion and motility is dependent on farnesylation. Catalytic @entity15931 mutants ( @entity71966 or @entity71967 ) were impaired in @entity15931 -induced invasion and Rho activation, indicating that these properties require phosphatase activity. We conclude that PRL PTPs stimulate Rho signaling pathways to promote motility and invasion. Characterization of PRL activity and regulatory pathways should enhance efforts to understand and interfere with PRL-mediated events in invasion and @entity3 .
