PKA-dependent phosphorylation of IP3K-A at Ser119 regulates a binding affinity with EB3

Biochem Biophys Res Commun. 2019 Jan 1;508(1):52-59. doi: 10.1016/j.bbrc.2018.11.042. Epub 2018 Nov 20.


Microtubule-associated end-binding protein 3 (EB3) accumulates asymmetrically at the tip-end of growing microtubules, providing a central platform for linking various cellular components. EB3 orchestrates microtubule dynamics and targeting, enabling diverse processes within neurons. Inositol 1, 4, 5-trisphosphate 3-kinase A (IP3K-A; also known as ITPKA) is a neuron-enriched protein that binds to microtubules by PKA-dependent manners. In this study, we found that IP3K-A binds to EB3 and their binding affinity is precisely regulated by protein kinase A (PKA)-dependent phosphorylation of IP3K-A at Ser119 (pSer119). We also revealed that the complex of IP3K-A and EB3 dissociates and reassociates rapidly during chemically induced LTP (cLTP) condition. This dynamic rearrangement of IP3K-A and EB3 complex will contribute remodeling of microtubule cytoskeleton allowing effective structural plasticity in response to synaptic stimulations.

Keywords: Cytoskeleton; EB3; IP3K-A; Neuron; PKA; Phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • HEK293 Cells
  • Humans
  • Long-Term Potentiation
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Neurons / metabolism
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Interaction Domains and Motifs
  • Rats
  • Serine / chemistry


  • MAPRE3 protein, human
  • Microtubule-Associated Proteins
  • Serine
  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Cyclic AMP-Dependent Protein Kinases