Integrin alpha1beta1 mediates a unique collagen-dependent proliferation pathway in vivo.
Activation of integrins upon binding to extracellular matrix proteins is believed to be a crucial step for the regulation of cell survival and proliferation. We have used integrin alpha1-null mice to investigate the role of this collagen receptor in the regulation of cell growth and survival in vivo. alpha1-deficient animals, which are viable and fertile, have a hypocellular dermis and a deficiency in dermal fibroblast proliferation as embryos. In vitro analysis of alpha1-null embryonic fibroblasts has revealed that their proliferation rate is markedly reduced when plated on collagenous substrata, despite normal attachment and spreading. Moreover, on the same collagenous matrices, alpha1-null fibroblasts fail to recruit and activate the adaptor protein Shc. The failure to activate Shc is accompanied by a downstream deficiency in recruitment of Grb2 and subsequent mitogen-activated protein kinase activation. Taken together with the growth deficiency observed on collagens, this finding indicates that the alpha1beta1 is the sole collagen receptor which can activate the Shc mediated growth pathway. Thus, integrin alpha1 has a unique role among the collagen receptors in regulating both in vivo and in vitro cell proliferation in collagenous matrices.
Pozzi
A
A
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Wary
K K
KK
Giancotti
F G
FG
Gardner
H A
HA
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D012867:Skin / Q000166:cytology / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D016023:Integrins; D011506:Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D003094:Collagen; D017871:Calcium-Calmodulin-Dependent Protein Kinases