Disease relevance of PDK1

• We now show that AtPDK1, expressed in E. coli as a recombinant protein, undergoes autophosphorylation at several sites [1].

High impact information on PDK1

• Plant hormones, auxin and cytokinin, synergistically activate the AtPDK1-regulated AGC2-1 kinase, indicative of a role in growth and cell division [2].
• Here we report on a lipid-signalling pathway in plants that is downstream of phosphatidic acid and involves the Arabidopsis protein kinase, AGC2-1, regulated by the 3'-phosphoinositide-dependent kinase-1 (AtPDK1) [2].
• We show that a PID activation loop serine is required for PDK1-dependent PID phosphorylation [3].
• PID immunoprecipitated from Arabidopsis cells in which PDK1 expression was inhibited by RNAi showed a dramatic reduction in transphosphorylation of myelin basic protein substrate [3].
• Mutation of Ser-276 in AtPDK1 to alanine resulted in an enzyme with no detectable autophosphorylation [1].

Biological context of PDK1

• The Arabidopsis AGC kinases contain sequence motives required for the docking of PDK1 and phosphorylation of their activation loop in the kinase catalytic domain [4].
• Phosphoinositide-dependent kinase-1 (PDK1) mediates activation of many AGC kinases by docking onto a phosphorylated hydrophobic motif located C-terminal of the catalytic domain in the AGC kinase [5].
• AtPDK1 is ubiquitously expressed in all plant tissues, whereas expression of AGC2-1 is abundant in fast-growing organs and dividing cells, and activated during re-entry of cells into the cell cycle after sugar starvation-induced G1-phase arrest [2].
• These results indicate that AtPDK1 is a potent enhancer of PID activity and provide evidence that phospholipid signaling may play a role in the signaling processes controlling polar auxin transport [3].
• Analysis of the primary amino-acid sequences of PDK from various sources reveals that these enzymes include the five domains characteristic of prokaryotic two-component His-kinases, despite the fact that PDK exclusively phosphorylates Ser residues in the E1alpha subunit of the PDC [6].

Analytical, diagnostic and therapeutic context of PDK1

• Furthermore, site-directed mutagenesis of the two most likely phosphotransfer His residues (H121 and H168) did not abolish either PDK autophosphorylation or the ability to transphosphorylate E1alpha [6].

References