PTEN protein phosphatase activity regulates metastasis by targeting PKCδ.

ABSTRACT: PTEN acts as a tumor suppressor through its lipid and protein phosphatase activities. We previously reported that PTEN phosphatase inhibits metastasis independent of its lipid phosphatase. To determine PTEN phosphatase downstream substrates and their role precisely in metastatic suppression, we used proteomic approaches to identify PKCδ as PTEN protein phosphatase substrates. We show that the inactivation of PTEN protein phosphatase activity causes loss of the capability to dephosphorylate PKCδ at S643, T505, and Y311, but wild-type or PTEN lipid phosphatase deficient mutants can maintain. We then established knock-in and knock-out models to confirm that PTEN protein phosphatase is required to inhibit PKCδ phosphorylation and necessary to suppress tumor metastasis. Notably, we found

SUBMITTER: Yu Y 

PROVIDER: S-EPMC12179624 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature