Phosphorylation of p27(KIP1) homologs KRP6 and 7 by SNF1-related protein kinase-1 links plant energy homeostasis and cell proliferation

Plant J. 2013 Aug;75(3):515-25. doi: 10.1111/tpj.12218. Epub 2013 Jun 13.

Abstract

SNF1-related protein kinase-1 (SnRK1), the plant kinase homolog of mammalian AMP-activated protein kinase (AMPK), is a sensor that maintains cellular energy homeostasis via control of anabolism/catabolism balance. AMPK-dependent phosphorylation of p27(KIP1) affects cell-cycle progression, autophagy and apoptosis. Here, we show that SnRK1 phosphorylates the Arabidopsis thaliana cyclin-dependent kinase inhibitor p27(KIP1) homologs AtKRP6 and AtKRP7, thus extending the role of this kinase to regulation of cell-cycle progression. AtKRP6 and 7 were phosphorylated in vitro by a recombinant activated catalytic subunit of SnRK1 (AtSnRK1α1). Tandem mass spectrometry and site-specific mutagenesis identified Thr152 and Thr151 as the phosphorylated residues on AtKRP6- and AtKRP7, respectively. AtSnRK1 physically interacts with AtKRP6 in the nucleus of transformed BY-2 tobacco protoplasts, but, in contrast to mammals, the AtKRP6 Thr152 phosphorylation state alone did not modify its nuclear localization. Using a heterologous yeast system, consisting of a cdc28 yeast mutant complemented by A. thaliana CDKA;1, cell proliferation was shown to be abolished by AtKRP6(WT) and by the non-phosphorylatable form AtKRP6(T152A) , but not by the phosphorylation-mimetic form AtKRP6(T152D). Moreover, A. thaliana SnRK1α1/KRP6 double over-expressor plants showed an attenuated AtKRP6-associated phenotype (strongly serrated leaves and inability to undergo callogenesis). Furthermore, this severe phenotype was not observed in AtKRP6(T152D) over-expressor plants. Overall, these results establish that the energy sensor AtSnRK1 plays a cardinal role in the control of cell proliferation in A. thaliana plants through inhibition of AtKRP6 biological function by phosphorylation.

Keywords: Arabidopsis thaliana; Kip-related protein; SNF1-related protein kinase-1; cell proliferation; energy homeostasis; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arabidopsis / cytology
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Energy Metabolism*
  • Gene Expression Regulation, Plant
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Threonine / metabolism

Substances

  • Arabidopsis Proteins
  • CDKN1B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • KRP6 protein, Arabidopsis
  • KRP7 protein, Arabidopsis
  • Cyclin-Dependent Kinase Inhibitor p27
  • Threonine
  • Protein Serine-Threonine Kinases
  • SnRK1 protein, Arabidopsis