Identification of proteins that interact with Siglec-6

ABSTRACT: Siglec-6 is a glycoprotein overexpressed on chronic lymphocytic leukemia (CLL) cell. We have shown that Siglec-6 promotes migration and adhesion of CLL cells towards CLL bone marrow stromal cells. To elucidate the mechanistic pathway involved in Siglec-6 dependent migration, we performed mass spectrometry proteomics analysis on MEC1-002 CLL cell line pulled down with a Siglec-6 targeted antibody, which revealed that Siglec-6 interacts with DOCK8, a guanine nucleotide exchange factor. Interaction of Siglec-6 with its ligand promotes DOCK8 dependent Cdc42 activation, WASP protein recruitment and F-actin polymerization. Therapeutically, Siglec-6 leukemic cells can be eliminated with a Siglec-6 targeted bispecific antibody in vitro and in vivo.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

DISEASE(S): Chronic Lymphocytic Leukemia

SUBMITTER: Jessica Nunes  

LAB HEAD: Natarajan Muthusamy

PROVIDER: PXD039892 | Pride | 2024-05-08

REPOSITORIES: Pride