Cytokine‐inducible SH2 protein‐3 (CIS3/SOCS3) inhibits <i>Janus</i> tyrosine kinase by binding through the N‐terminal kinase inhibitory region as well as SH2 domain

Abstract

CIS3 inhibits JAK2 kinase activity by binding to the activation loop through the SH2 domain, and KIR is necessary for kinase inhibition. Although the inhibitory mechanism by CIS3 is similar to that by JAB, the contributions of the SH2 domain and KIR for binding are different between JAB and CIS3. Our study defined the inhibitory mechanism of CIS3 and provides a useful information for creating a novel tyrosine kinase inhibitor.