Differential regulation of Rho GTPases by beta1 and beta3 integrins: the role of an extracellular domain of integrin in intracellular signaling.
Integrins mediate cell adhesion and signal transduction at focal adhesions. Here we investigate the roles of integrin beta subunits in the regulation of actin cytoskeletal structure and the activities of Rho and Rac. The overexpression of beta3 integrin in Chinese hamster ovary cells enhances Rho activity and stress fiber formation, whereas the overexpression of beta1 integrin increases Rac activity and lamellipodia formation. The overexpression of a mutant beta1-3-1 integrin, in which the extracellular I-domain-like sequence of beta1 integrin has been replaced with the corresponding sequence of beta3 integrin, also enhances Rho activity and the formation of stress fibers. Our results demonstrate that beta1 and beta3 integrins differentially regulate the activities of Rho family GTPases and that the extracellular domains of integrin beta subunits play a critical role in transducing the extracellular ligand-binding information into specific intracellular signaling events.
Miao
Hui
H
Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla 92093-0427, USA.
Li
Song
S
Hu
Ying-Li
YL
Yuan
Suli
S
Zhao
Yihua
Y
Chen
Benjamin P C
BP
Puzon-McLaughlin
Wilma
W
Tarui
Takehiko
T
Shyy
John Y-J
JY
Takada
Yoshikazu
Y
Usami
Shunichi
S
Chien
Shu
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D048429:Cell Size; D006224:Cricetinae; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry* / Q000378:metabolism*; D039661:Integrin beta3 / Q000737:chemistry* / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D005353:Fibronectins; D019012:Integrin beta1; D039661:Integrin beta3; D005340:Fibrinogen; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins