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PMID:11118207

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Citation

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. 19:6721-31

Abstract

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced signaling, its biological role has remained unknown. Fibroblasts homozygous for expression of an SHPS-1 mutant lacking most of the cytoplasmic region of this protein exhibited increased formation of actin stress fibers and focal adhesions. They spread more quickly on fibronectin than did wild-type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion-induced activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras-extracellular signal-regulated kinase signaling pathway and of c-Jun N-terminal kinases by growth factors was either unaffected or enhanced in the mutant fibroblasts. These results demonstrate that SHPS-1 plays crucial roles in integrin-mediated cytoskeletal reorganization, cell motility and the regulation of Rho, and that it also negatively modulates growth factor-induced activation of mitogen-activated protein kinases.

Links

PubMed PMC305898 Online version:10.1093/emboj/19.24.6721

Keywords

Animals; Antigens, Differentiation; Cell Adhesion; Cell Line; Cell Movement/physiology; Cytoskeleton/physiology; Cytoskeleton/ultrastructure; Exons; Extracellular Matrix/physiology; GTP Phosphohydrolases/metabolism; Genomic Library; Integrins/physiology; Membrane Glycoproteins/chemistry; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecules/chemistry; Neural Cell Adhesion Molecules/genetics; Neural Cell Adhesion Molecules/physiology; Receptors, Immunologic; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Recombination, Genetic; Sequence Deletion; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2388979

P

Seeded From UniProt

complete

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0007015: actin filament organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2388979

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0007010: cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2388979

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete


See also

References

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