KIT D816V is dimerization‐independent and activates downstream pathways frequently perturbed in mastocytosis

• DOI: 10.1111/bjh.18116
• Publication Date: 2022-03-04T18:26:54Z
• Authors: Vinothkumar Rajan; Sergey V. Prykhozhij; Aditya Pandey; Alejandro M. Cohen; Jan K. Rainey; Jason N. Berman
• Keywords: Proto-Oncogene Proteins c-kit

Abstract KIT, a type III tyrosine kinase receptor, plays crucial role in haematopoietic development. The KIT receptor forms dimer after ligand binding; this activates activity leading to downstream signal transduction. D816V mutation is extensively implicated haematological malignancies, including mastocytosis and leukaemia. constitutively active, but the molecular nuances that lead constitutive are unclear. For first time, we present experimental evidence mutant does not dimerize like wild type. We further show of decreased stabilization domain mutant, phenomenon might contribute its activity. Since mechanism activation varies from type, explored transduction events found even though targets similar signalling moieties, amplified compared stem cell factor‐activated receptor. Uniquely, induces infection‐related pathways spliceosome pathway, providing alternate options for selective as well combinatorial therapeutic targeting.