Editors' ChoiceCell Biology

SHPS-1 and Cell Migration

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Science's STKE  09 Jan 2001:
Vol. 2001, Issue 64, pp. tw12
DOI: 10.1126/stke.2001.64.tw12

SHPS-1 (SH2 domain-containing protein tyrosine phosphatase substrate 1) is a glycosylated transmembrane protein containing four potential SH2 domain binding sites, and SHPS-1 has been implicated in signal transduction. The phosphatases SHP-1 and SHP-2 bind to SHPS-1 and regulate signals from growth factor receptors. However, the exact role of SHPS-1 in the cell remains unknown. Inagaki et al. investigated the role of SHPS-1 by creating cell lines expressing a SHPS-1 cytoplasmic domain deletion mutant (SHPS-1Δcyto). Fibroblasts expressing SHPS-1Δcyto exhibited an epithelial-like morphology and had increased numbers of focal adhesions and stress fibers. Transfection of wild-type SHPS-1 into SHPS-1Δcyto mutant cells caused reversion to fibroblast morphology. Cells expressing SHPS-1Δcyto exhibited an increased capacity for spreading; however, cell migration was decreased, as measured by an in vitro wound healing assay. Tyrosine phosphorylation of FAK (focal adhesion kinase) and Cas and activation of the small guanosine triphosphatase (GTPase) Rac were unaffected in the mutant cells. However, activation of the GTPase Rhos was almost completely blocked in mutant cells treated with LPS (lipopolysaccharide), a known Rho activator. Because Rho can act downstream of SHP-2 in some model systems, the authors suggest that the decreased migration of SHPS-1Δcyto-expressing cells results from the inability of SHPS-1Δcyto to bind SHP-2 and, subsequently, the lack of Rho activation. Thus, one role for SHPS-1 may be to regulate the architecture of the cytoskeletal network.

Inagaki, K., Yamao, T., Noguchi, T., Matozaki, T., Fukunaga, K., Takada, T., Hosooka, T., Akira, S., and Kasuga, M. (2000) SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. EMBO J. 24: 6721-6731. [Abstract] [Full Text]

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