THE ADAPTER PROTEIN NCK LINKS RECEPTOR TYROSINE KINASES WITH THE SERINE-THREONINE KINASE PAK1

Nck is an adaptor protein composed of a single SH2 domain and three SH 3 domains. Upon growth factor stimulation, Nck is recruited to recepto r tyrosine kinases via its SH2 domain, probably initiating one or more signaling cascades, In this report, we show that Nck is bound in livi ng cells to the serine-threonine kinase Pak1. The association between Nck and Pak1 is mediated by the second SH3 domain of Nck and a proline -rich sequence in the amino terminus of Pak1. We also show that Pak1 i s recruited by activated epidermal growth factor (EGF) and platelet-de rived growth factor receptors, Moreover, Pak1 kinase activity is incre ased in response to EGF in HeLa cells transfected with human Pak1, and the kinase activity was enhanced when Nck was co-transfected. It is c oncluded that Nck links receptor tyrosine kinases with Pak1 and is pro bably involved in targeting and regulation of Pak1 activity.