Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain

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Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain. / Hirsch, E; Barberis, L; Brancaccio, M; Azzolino, O; Xu, DZ; Kyriakis, JM; Silengo, L; Giancotti, FG; Tarone, G; Fässler, Reinhard; Altruda, F.

I: Journal of Cell Biology, Vol. 157, Nr. 3, 2002, s. 481-492.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Hirsch, E, Barberis, L, Brancaccio, M, Azzolino, O, Xu, DZ, Kyriakis, JM, Silengo, L, Giancotti, FG, Tarone, G, Fässler, R & Altruda, F 2002, 'Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain', Journal of Cell Biology, vol. 157, nr. 3, s. 481-492. https://doi.org/10.1083/jcb.200111065

APA

Hirsch, E., Barberis, L., Brancaccio, M., Azzolino, O., Xu, DZ., Kyriakis, JM., Silengo, L., Giancotti, FG., Tarone, G., Fässler, R., & Altruda, F. (2002). Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain. Journal of Cell Biology, 157(3), 481-492. https://doi.org/10.1083/jcb.200111065

CBE

Hirsch E, Barberis L, Brancaccio M, Azzolino O, Xu DZ, Kyriakis JM, Silengo L, Giancotti FG, Tarone G, Fässler R, Altruda F. 2002. Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain. Journal of Cell Biology. 157(3):481-492. https://doi.org/10.1083/jcb.200111065

MLA

Vancouver

Author

Hirsch, E ; Barberis, L ; Brancaccio, M ; Azzolino, O ; Xu, DZ ; Kyriakis, JM ; Silengo, L ; Giancotti, FG ; Tarone, G ; Fässler, Reinhard ; Altruda, F. / Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain. I: Journal of Cell Biology. 2002 ; Vol. 157, Nr. 3. s. 481-492.

RIS

TY - JOUR

T1 - Defective Rac-mediated proliferation and survival after targeted mutation of the beta(1) integrin cytodomain

AU - Hirsch, E

AU - Barberis, L

AU - Brancaccio, M

AU - Azzolino, O

AU - Xu, DZ

AU - Kyriakis, JM

AU - Silengo, L

AU - Giancotti, FG

AU - Tarone, G

AU - Fässler, Reinhard

AU - Altruda, F

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Pathology (013031100), Pathology, (Lund) (013030000)

PY - 2002

Y1 - 2002

N2 - Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of beta(1) integrin leads to defective proliferation and survival both in vivo and in vitro. Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-P13K-Akt and Rac-JNK signaling pathways. Expression in homozygous MEFs of a constitutively active form of Rac is able to rescue proliferation, survival, and JNK activation. Moreover, although showing normal Erk phosphorylation, mutant cells fail to display Erk nuclear translocation upon fibronectin adhesion. However, expression of the constitutively activated form of Rac restores Erk nuclear localization, suggesting that adhesion-dependent Rac activation is necessary to integrate signals directed to promote MAPK activity. Altogether, our data provide the evidence for an epistatic interaction between the beta(1) integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control.

AB - Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of beta(1) integrin leads to defective proliferation and survival both in vivo and in vitro. Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-P13K-Akt and Rac-JNK signaling pathways. Expression in homozygous MEFs of a constitutively active form of Rac is able to rescue proliferation, survival, and JNK activation. Moreover, although showing normal Erk phosphorylation, mutant cells fail to display Erk nuclear translocation upon fibronectin adhesion. However, expression of the constitutively activated form of Rac restores Erk nuclear localization, suggesting that adhesion-dependent Rac activation is necessary to integrate signals directed to promote MAPK activity. Altogether, our data provide the evidence for an epistatic interaction between the beta(1) integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control.

KW - cytodomain

KW - integrin

KW - MAPK

KW - RAC

KW - proliferation

U2 - 10.1083/jcb.200111065

DO - 10.1083/jcb.200111065

M3 - Article

VL - 157

SP - 481

EP - 492

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 3

ER -