The Src-family kinase Lck can induce STAT3 phosphorylation and DNA bindingactivity

Constitutive activation of the Src-family kinase Lck has been shown to lead to transformation. Constitutive activation of the STAT pathway of transcri ption factors has also been shown to be involved in transformation. An onco genic form of the prototypical member of the Src-family, v-Src, has been sh own to activate STAT3, and this activation is required for v-Src's transfor ming ability. To investigate whether Lck could directly activate STAT3, a b aculovirus expression system was utilised. When Lck and STAT3 were coexpres sed, STAT3 was found to have enhanced tyrosine phosphorylation and DNA bind ing activity. This finding was confirmed with experiments where exogenous L ck was added to baculovirus produced STAT3. Moreover, the activation of STA T3 by exogenous Lck could be attenuated by the Lck-specific inhibitor PP1. In addition, mammalian cells stably expressing a constitutively activated f orm of Lck were shown to have activated STAT3. These data provide strong ev idence that, like v-Src, Lck can also directly activate STAT3, which contri butes to the transformation process. (C) 1999 Elsevier Science Inc.