Phospholipase D2 (PLD2) (PLD2)

Phospholipase D2 (PLD2) is a membrane-associated enzyme that catalyzes the hydrolysis of phosphatidylcholine to generate the second messenger phosphatidic acid (PA) and choline (UniProt P48591). In keratinocytes, PLD2 is a crucial regulator of calcium-induced differentiation, a process essential for maintaining the skin's protective barrier (PubMed: 11514544). Dysregulation of PLD2 signaling is implicated in hyperproliferative and inflammatory skin conditions such as psoriasis, where elevated PA levels drive aberrant cell growth (PubMed: 23454751). Pharmacological inhibition of PLD2 using small molecules like VU0364739 or the dual PLD1/2 inhibitor FIPI has shown potential in modulating these pathways and reducing inflammatory cytokine production (PubChem CID: 44141410). Beyond the skin, PLD2 is involved in cancer cell migration and protein trafficking, making it a target of interest for both dermatological and oncological applications (PubMed: 21135165). The enzyme's activity is often regulated by Rho-family GTPases and protein kinase C, integrating it into complex cellular signaling networks. Therapeutic strategies focusing on PLD2 aim to restore normal keratinocyte homeostasis in diseased skin.

Other names

Phosphatidylcholine-specific phospholipase D2PLD 2hPLD2Phospholipase D2 in keratinocytes

Inhibition of the enzymatic hydrolysis of phosphatidylcholine to phosphatidic acid and choline, thereby modulating lipid-mediated signaling pathways involved in keratinocyte differentiation and proliferation.