Thymosin beta4 is involved in stabilin-2-mediated apoptotic cell engulfment.

Stabilin-2 was recently identified as a novel receptor for membrane phosphatidylserine of apoptotic cells. To identify proteins that were candidates for stabilin-2 cytoplasmic domain binding, we screened a human spleen cDNA library using the yeast two-hybrid system. We found that thymosin beta4 interacts with the stabilin-2 cytoplasmic domain and is co-localized with stabilin-2 at the phagocytic cup. Knockdown of thymosin beta4 significantly decreased the phagocytic activity of stabilin-2, whereas overexpression of thymosin beta4 increased this activity. Additionally, amino acids 2504-2514 of stabilin-2 cytoplasmic domain were found to be responsible for the interaction with thymosin beta4. Taken together, these results suggest that thymosin beta4 is a downstream molecule of stabilin-2 that plays a role in stabilin-2-mediated cell corpse clearance.