Pak1 protein kinase regulates activation and nuclear localization of Snf1-Gal83 protein kinase.

Three kinases, Pak1, Tos3, and Elm1, activate Snf1 protein kinase in Saccharomyces cerevisiae. This cascade is conserved in mammals, where LKB1 activates AMP-activated protein kinase. We address the specificity of the activating kinases for the three forms of Snf1 protein kinase containing the beta-subunit isoforms Gal83, Sip1, and Sip2. Pak1 ...
is the most important kinase for activating Snf1-Gal83 in response to glucose limitation, but Elm1 also has a significant role; moreover, both Pak1 and Elm1 affect Snf1-Sip2. These findings exclude the possibility of a one-to-one correspondence between the activating kinases and the Snf1 complexes. We further identify a second, unexpected role for Pak1 in regulating Snf1-Gal83: the catalytic activity of Pak1 is required for the nuclear enrichment of Snf1-Gal83 in response to carbon stress. The nuclear enrichment of Snf1 fused to green fluorescent protein (GFP) depends on both Gal83 and Pak1 and is abolished by a mutation of the activation loop threonine; in contrast, the nuclear enrichment of Gal83-GFP occurs in a snf1Delta mutant and depends on Pak1 only when Snf1 is present. Snf1-Gal83 is the only form of the kinase that localizes to the nucleus. These findings, that Pak1 both activates Snf1-Gal83 and controls its nuclear localization, implicate Pak1 in regulating nuclear Snf1 protein kinase activity.
Mesh Terms:
AMP-Activated Protein Kinases, Base Sequence, Cell Nucleus, DNA, Fungal, Enzyme Activation, Fungal Proteins, Genes, Fungal, Mutagenesis, Site-Directed, Mutation, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Threonine, Trans-Activators, p21-Activated Kinases
Mol. Cell. Biol.
Date: Sep. 01, 2004
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