PLATELET-DERIVED GROWTH FACTOR-INDUCED FORMATION OF TENSIN AND PHOSPHOINOSITIDE 3-KINASE COMPLEXES

Tensin is an SH2 domain-containing cytoskeletal protein that binds to and caps actin filaments. Investigation of signal transduction mechani sms associated with tensin revealed the presence of phosphoinositide 3 -kinase (PI 3-kinase) activity in tensin immunoprecipitates from plate let derived growth factor-treated cells. Association of PI 3-kinase ac tivity with tensin was transitory, and the amount of activity was appr oximately 1% of the total PI 3-kinase activity found in anti-phosphoty rosine (anti-pY) immunoprecipitates. In vitro, PI 3-kinase activity as sociated with the SH2 domain of tensin in a platelet-derived growth fa ctor-dependent manner. The optimal phosphopeptide binding specificity of the SH2 domain of tensin was determined to be phospho-Y (E or D), N , (I, V, or F). Synthetic phosphopeptides containing the sequence YENI could specifically block the association of PI 3-kinase activity with tensin in a dose dependent manner. These results suggest that PI 3-ki nase interacts with the cytoskeleton via the SH2 domain of tensin and may play an important role in platelet-derived growth factor-induced c ytoskeletal reorganization that is concomitant with cell migration and proliferation.