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Review
. 2006 Oct;1763(10):991-9.
doi: 10.1016/j.bbamcr.2006.08.008. Epub 2006 Aug 18.

Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses

Tanya A Rege  1 , James S Hagood
Affiliations
Review

Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses

Tanya A Rege et al. Biochim Biophys Acta. 2006 Oct.

Abstract

Thy-1 is a 25-37 kDa glycosylphosphatidylinositol (GPI)-anchored protein involved in T cell activation, neurite outgrowth, apoptosis, tumor suppression, wound healing, and fibrosis. To mediate these diverse effects, Thy-1 participates in multiple signaling cascades. In this review, we discuss Thy-1 signaling primarily in non-immunologic cell types, including neurons, mesangial cells, ovarian cancer cells, nasopharyngeal carcinoma cells, endothelial cells, and fibroblasts. We review the current literature regarding Thy-1 signaling via integrins, protein tyrosine kinases, and cytokines and growth factors; and the roles of these signaling pathways in cellular adhesion, apoptosis, cell proliferation, and cell adhesion and migration. We also discuss the role of Thy-1 localization to lipid rafts, and of the GPI anchor in Thy-1 signaling. Ongoing research on the mechanisms of Thy-1 signaling will add to our understanding of the diverse physiologic and pathologic processes in which Thy-1 plays a role.

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Figures

Fig. 1
Fig. 1
Schematic of Thy-1-associated signaling pathways. (A) Thy-1 interacts with both β2 and β3 integrins. The association of neuronal Thy-1 with β3 on astrocytes induces activation of FAK, vinculin, paxillin, p130Cas, and RhoA, promoting focal adhesion and stress fiber formation. This interaction may induce bidirectional signaling by concurrently signaling an inhibition of neurite outgrowth in mature neurons. Endothelial cell Thy-1 also interacts with β2 on leukocytes and β3 on melanoma cells to promote transendothelial cell migration in vitro. (B) Thy-1 associates with protein tyrosine kinases such as SFK within lipid rafts. This interaction may induce apoptosis of glomerular mesangial cells, promote neurite outgrowth in neurons, inhibit migration of pulmonary fibroblasts by altering the cytoskeleton, and promote T cell activation. (C) Thy-1 activation induces apoptosis in thymocytes, glomerular mesangial cells, and mouse malignant T cells. In malignant T cells, Thy-1 activation activates caspases and downregulates anti-apoptotic bcl-2 and bcl-XL. In an anti-Thy-1-induced model of glomerulonephritis, the apoptosis-related genes NGFI-B and Gadd 45 γ are upregulated. In this same model, the expression of cell cycle regulatory proteins is also modulated (see text for details). (D) Thy-1 promotes proliferation of mesangial cells via activation of Smad1 and STAT3, and proliferation of T cells through a pathway involving calcineurin, protein tyrosine kinases, PI-3 kinase, protein kinase C, and MAPK. Thy-1 also promotes TGF-β activation, cytokine/growth factor signaling, eicosanoid production, and myofibroblasts/lipofibroblast differentiation. (E) Thy-1 functions as tumor suppressor in nasopharyngeal carcinoma and ovarian cancer cells, potentially due to its upregulation of thrombospondin-1 and fibronectin. * indicates that Thy-1 cross-linking is necessary for effect.
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