Protein arginine methyltransferase 5 (PRMT5) signaling suppresses protein kinase C?- and p38?-dependent signaling and keratinocyte differentiation.

ABSTRACT: PKC? is a key regulator of keratinocyte differentiation that activates p38? phosphorylation leading to increased differentiation as measured by an increased expression of the structural protein involucrin. Our previous studies suggest that p38? exists in association with protein partners. A major goal is to identify these partners and understand their role in regulating keratinocyte differentiation. In this study we use affinity purification and mass spectrometry to identify protein arginine methyltransferase 5 (PRMT5) as part of the p38? signaling complex. PRMT5 is an arginine methyltransferase that symmetrically dimethylates arginine residues on target proteins to alter target protein function. We show that PRMT5 knockdown is associated with increased p38? phosphorylation, suggesting that PRMT5 impacts the p38? signaling complex. At a functional level we show that PRMT5 inhibits the PKC?- or 12-O-tetradecanoylphorbol-13-acetate-dependent increase in human involucrin expression, and PRMT5 dimethylates proteins in the p38? complex. Moreover, PKC? expression reduces the PRMT5 level, suggesting that PKC? activates differentiation in part by reducing PRMT5 level. These studies indicate antagonism between the PKC? and PRMT5 signaling in control of keratinocyte differentiation.

SUBMITTER: Kanade SR 

PROVIDER: S-EPMC3293539 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature