Pleiotrophin stimulates tyrosine phosphorylation in NIH 3T3 and NB41A3 cells.

Pleiotrophin (PTN) is a heparin-binding cytokine that functions as a neurite outgrowth promoting and mitogenic activity in vitro. PTN is highly conserved and its gene is widely expressed in mammalian tissues during development, suggesting important roles of PTN in vivo. However, the mechanisms by which PTN mediates its functional activities are unknown. We now report that an approximately 200 kDa (p200) protein is phosphorylated (pp200) in PTN stimulated NIH 3T3 and NB41A3 cells five minutes after stimulation with PTN. Phosphorylation is maximum at 15 minutes and is PTN concentration dependent. pp200 is recognized by antiphosphotyrosine antibodies and contains both phosphotyrosine and phosphoserine by phosphoamino acid analysis. The results suggest that PTN functions in part through activation of protein kinase(s) in NIH 3T3 and NB41A3 cells.