The PI 3‐kinase/Akt pathway plays a role in the trafficking of the surfactant protein‐A (SP‐A) receptor P63 (CKAP4) to the cell surface of type II pneumocytes

Abstract

P63 (CKAP4), a 63 kDa type II transmembrane protein, is an SP‐A receptor on type II pneumocytes. An antibody to P63 previously has been shown to block both the specific binding of SP‐A to pneumocytes and the ability of SP‐A to regulate surfactant secretion. In the current work, the P63 antibody blocked the ability of SP‐A to stimulate surfactant uptake by pneumocytes. P63 is located on both the plasma membrane (PM) and the endoplasmic reticulum (ER). Cyclic AMP exposure resulted in enrichment of P63 on the cell surface as shown by stimulation of SP‐A binding; enhanced association of labeled P63 antibody with type II cells; and promotion of SP‐A‐mediated liposome uptake, all of which were inhibited by competing P63 antibody. Treatment of type II cells with LY294002, an inhibitor of the phosphatidylinositol‐3‐kinase (PI3‐kinase) signaling pathway, prevented the SP‐A‐induced PM enrichment of P63. Exposure of pneumocytes to SP‐A or cAMP activated Akt (protein kinase B). Blocking either PI3‐kinase or Akt with inhibitors prevented SP‐A‐mediated lipid turnover. The data demonstrate an important role for the PI3‐kinase/Akt signaling pathway in the intracellular trafficking of P63. The results add further evidence that P63 is critical for SP‐A receptor‐mediated interactions with type II pneumocytes and the resultant regulation of surfactant turnover. [HL 19737]