Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase

Biochem J. 2000 Nov 1;351 Pt 3(Pt 3):551-5.


We describe a human cDNA encoding 1-kinase activity that inactivates Ins(3,4,5,6)P(4), an inhibitor of chloride-channel conductance that regulates epithelial salt and fluid secretion, as well as membrane excitability. Unexpectedly, we further discovered that this enzyme has alternative positional specificity (5/6-kinase activity) towards a different substrate, namely Ins(1,3,4)P(3). Kinetic data from a recombinant enzyme indicate that Ins(1,3,4)P(3) (K(m)=0.3 microM; V(max)=320 pmol/min per microg) and Ins(3,4,5,6)P(4) (K(m)=0.1 microM; V(max)=780 pmol/min per microg) actively compete for phosphorylation in vivo. This competition empowers the kinase with multitasking capability in several key aspects of inositol phosphate signalling.

MeSH terms

  • Base Sequence
  • DNA Primers
  • Escherichia coli / genetics
  • Humans
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction*


  • DNA Primers
  • Recombinant Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • inositol-tetrakisphosphate 1-kinase
  • myo-inositol-trisphosphate 6-kinase