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Sci. STKE, 9 January 2001
Vol. 2001, Issue 64, p. tw12
[DOI: 10.1126/stke.2001.64.tw12]


Cell Biology SHPS-1 and Cell Migration

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-1{Delta}cyto). Fibroblasts expressing SHPS-1{Delta}cyto exhibited an epithelial-like morphology and had increased numbers of focal adhesions and stress fibers. Transfection of wild-type SHPS-1 into SHPS-1{Delta}cyto mutant cells caused reversion to fibroblast morphology. Cells expressing SHPS-1{Delta}cyto 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-1{Delta}cyto-expressing cells results from the inability of SHPS-1{Delta}cyto 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]

Citation: SHPS-1 and Cell Migration. Sci. STKE 2001, tw12 (2001).

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