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

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 subce...

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Bibliographic Details
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
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.04.101