Pak1 protein kinase regulates both activation and nuclear localization of Snf1-Gal83 protein kinase.
Kristina Hedbacker, Seung-Pyo Hong, Marian Carlson
Genetics and Development, Columbia University, 701 W 168th St, New York, NY, 10032, USA
The Snf1 protein kinase is important for transcriptional, metabolic, and developmental responses to stress, notably carbon stress. Three upstream kinases, Pak1, Elm1, and Tos3, activate Snf1 by phosphorylating the activation-loop threonine; this cascade is conserved in mammals, and we identified LKB1 as an upstream kinase for AMP-activated protein kinase (PNAS 2003, 100, 8839). We have explored the roles of the upstream kinases in regulating Snf1 activity and localization. We addressed the specificity of the three upstream kinases for activating the three forms of Snf1 containing the different beta subunit isoforms, Gal83, Sip1 and Sip2. We found that Pak1 is the most important kinase for activating Snf1-Gal83 catalytic activity in response to carbon stress. We further identified a second role for Pak1 in regulating Snf1-Gal83: Pak1 is both necessary and sufficient for the nuclear enrichment of Snf1-Gal83 in response to carbon stress. Moreover, Pak1 regulates the localization of Gal83 by a mechanism that is independent of the Snf1 catalytic subunit. Snf1-Gal83 is the only form of the kinase that localizes to the nucleus; hence Pak1 exerts control at two different levels to regulate nuclear Snf1 protein kinase activity.
Return to YGM 2004 Home at SGD