Phosphorylation of heat shock protein 40 (Hsp40/DnaJB1) by mitogen-activated protein kinase-activated protein kinase 5 (MK5/PRAK)

Int J Biochem Cell Biol. 2014 Feb;47:29-37. doi: 10.1016/j.biocel.2013.11.004. Epub 2013 Dec 2.

Abstract

Heat shock protein 40 (Hsp40) acts as a co-chaperone with Hsp70 to promote protein folding, protein transport and degradation. The human Hsp40 family contains more than 40 members, some of which can exist as phosphoproteins in the cell. However, little is known about the protein kinases responsible for their phosphorylation and the functional relevance of this post-translational modification remains elusive. Here we show that Hsp40/DnaJB1 is an in vitro and in vivo substrate for the mitogen-activated protein kinase-activated protein kinase 5 (MK5). MK5 and Hsp40/DnaJB1 form complexes in cells and this interaction is accomplished by the C-terminal regions of both proteins. MK5 can phosphorylate Hsp40/DnaJB1 at several residues in vitro. Studies with specific phosphoantibodies indicate that MK5 phosphorylates Hsp40/DnaJB1 in vivo at Ser-149 or/and Ser-151 and Ser-171 in the C-terminal domain of Hsp40/DnaJB1. MK5 modestly stimulates the ATP hydrolyse activity of Hsp40/Hsp70 complex and enhances the repression of heat shock factor 1 driven transcription by Hsp40/DnaJB1.

Keywords: ATP hydrolysis; CREB; HSF; HSF1; HSP; MAPKAPK-5; MK; PK; PKA; PRAK; cAMP response element binding protein; cAMP-dependent protein kinase/protein kinase A; heat shock factor; heat shock protein; mitogen-activated protein kinase-activated protein kinase; protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • HEK293 Cells
  • HSP40 Heat-Shock Proteins / genetics
  • HSP40 Heat-Shock Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Transfection

Substances

  • DNAJB1 protein, human
  • HSP40 Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • MAP-kinase-activated kinase 5
  • Protein-Serine-Threonine Kinases
  • Adenosine Triphosphatases