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

TY - JOUR

T1 - The N2-Src neuronal splice variant of C-Src has altered SH3 domain ligand specificity and a higher constitutive activity than N1-Src

AU - Keenan, Sarah

AU - Lewis, Philip A

AU - Wetherill, Sarah J

AU - Dunning, Christopher J R

AU - Evans, Gareth J O

N1 - © 2015, The Authors. This content is made available by the publisher under a Creative Commons Attribution Licence. This means that a user may copy, distribute and display the resource providing that they give credit. Users must adhere to the terms of the licence.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - 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.

AB - 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.

U2 - 10.1016/j.febslet.2015.05.033

DO - 10.1016/j.febslet.2015.05.033

M3 - Article

C2 - 26026271

SN - 0014-5793

VL - 589

SP - 1995

EP - 2000

JO - FEBS Letters

JF - FEBS Letters

IS - 15

ER -