SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility.
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.
Inagaki
K
K
Second Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Yamao
T
T
Noguchi
T
T
Matozaki
T
T
Fukunaga
K
K
Takada
T
T
Hosooka
T
T
Akira
S
S
Kasuga
M
M
D000818:Animals; D000943:Antigens, Differentiation; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D005091:Exons; D005109:Extracellular Matrix / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D015698:Genomic Library; D016023:Integrins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic; D017384:Sequence Deletion; D015398:Signal Transduction
D000943:Antigens, Differentiation; D016023:Integrins; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases