SH3-mediated Hck Tyrosine Kinase Activation and Fibroblast Transformation by the Nef Protein of HIV-1

摘要: Tyrosine kinases of the Src family are regulated via their homology 2 (SH2) and SH3 domains. The Nef protein human immunodeficiency virus-1 (HIV-1) has previously been shown to bind with high affinity specificity in vitro domain Hck, a member expressed primarily myeloid cells. However, effect on Hck activity living cells is unknown. Here we show that Rat-2 fibroblasts co-expressing rapidly developed transformed foci, whereas control expressing either alone did not. formed stable complex stimulated its tyrosine kinase vivo. Mutagenesis proline-rich motif essential for binding completely blocked formation, activation, transformation, indicating SH3-binding function required effects Hck. These results provide direct evidence engagement sufficient activate kinasein vivo suggest may be activated by HIV-infected macrophages.