The N2-Src neuronal splice variant of C-Src has altered SH3 domain ligand specificity and a higher constitutive activity than N1-Src

FEBS Lett. 2015 Jul 8;589(15):1995-2000. doi: 10.1016/j.febslet.2015.05.033. Epub 2015 May 27.

Abstract

N2-Src is a poorly understood neuronal splice variant of the ubiquitous C-Src tyrosine kinase, containing a 17 amino acid insert in its Src homology 3 (SH3) domain. To characterise the properties of N2-Src we directly compared its SH3 domain specificity and kinase activity with C- and N1-Src in vitro. N2- and N1-Src had a similar low affinity for the phosphorylation of substrates containing canonical C-Src SH3 ligands and synaptophysin, an established neuronal substrate for C-Src. N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. Therefore, N2-Src is a highly active kinase that is likely to phosphorylate alternative substrates to C-Src in the brain.

Keywords: Enzyme kinetics; Kinase assay; Splice variant; Src; Src homology 3 domain; Tyrosine protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Ligands
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / chemistry
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • RNA Splicing*
  • Rats
  • Sequence Homology, Amino Acid
  • src Homology Domains*

Substances

  • Ligands
  • Protein Isoforms
  • Proto-Oncogene Proteins pp60(c-src)