SHIP interacts with adaptor protein Nck and restricts actin turnover in B cells

• Published in: Biochemical and biophysical research communications 2020-06, Vol.527 (1), p.207-212
• Main Authors: Pauls, Samantha D., Hou, Sen, Marshall, Aaron J.
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Adaptor Proteins, Signal Transducing - metabolism; Animals; B cell; B-Lymphocytes - metabolism; Humans; Inositol Polyphosphate 5-Phosphatases - genetics; Inositol Polyphosphate 5-Phosphatases - metabolism; Lymphocyte; Mice; Nck; Oncogene Proteins - metabolism; Receptors, Antigen, B-Cell - metabolism; SHIP; Spreading; src Homology Domains; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.04.101

SH2 domain-containing inositol 5′-phosphatase (SHIP) has critical functions in regulating signal transduction. In additional to its lipid phosphatase activity, SHIP engages in multiple protein-protein interactions, which can serve to localize either SHIP or its binding partners to a particular subcellular domain. Knock-out and knock-down studies have elucidated that SHIP negatively regulates the accumulation of F-actin in leukocytes, usually resulting in inhibition of actin dependent cellular activities such as spreading and migration. Here, we demonstrate that overexpression of SHIP inhibits B cell antigen receptor (BCR)-mediated cell spreading in murine and human B cell lines. B cell stimulation via the BCR or pervanadate induces an interaction between SHIP and Nck, an adaptor protein known to promote actin polymerization. Using a fluorescence recovery after photobleaching (FRAP) assay, we demonstrate that overexpression of SHIP slows F-actin dynamics in BCR-stimulated B cells and this can be overcome by co-overexpression of Nck. Our data supports a role for SHIP in limiting actin turnover and suggests it may do so in part by sequestering Nck. •Overexpression of SHIP impairs B cell spreading.•SHIP interacts with Nck in stimulated B cells.•SHIP-mediated inhibition of actin turnover is reversed by co-expression of Nck.