• FGF2 is able to directly interact with LYVE-1 and glycosylation of LYVE-1 is important for the interaction with FGF2.• LYVE-1 inhibits FGF2-dependent lymphangiogenesis and FGF2 modulates LYVE-1's endogenous expression and reverses the effect of TNF.LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) is a homolog of the hyaluronan receptor CD44, and one of the most widely used markers of lymphatic endothelial cells in normal and tumor tissues. However, the physiologic role of LYVE-1 in the lymphatic system still remains unclear. It is well established that fibroblast growth factor 2 (FGF2) induces lymphangiogenesis. Based on the known interaction between FGF2 and CD44 and based on the structural similarity of CD44 and LYVE-1, we investigated whether FGF2 might interact with LYVE-1. We found that FGF2 is able to bind LYVE-1 using AlphaScreen, or after surface-immobilization or in solution. FGF2 binds to LYVE-1 with a higher affinity than any other known LYVE-1-binding molecules, such as hyaluronan or PDGF-BB. Glycosylation of LYVE-1 is important for FGF2 binding. IntroductionThe lymphatic system is important to maintain fluid homeostasis by collecting fluid that leaks from capillary blood vessels and returning it to the blood circulation. 1 Perturbations in the development, maintenance and function of the lymphatic system can lead to a variety of pathologic lymphatic disorders including lymphedema, inflammation, and tumor metastasis. 2 The understanding of the molecular and cellular regulation of lymphangiogenesis has greatly advanced in recent years with the identification of the lymphangiogenic vascular endothelial growth factors VEGF-C and VEGF-D and their lymphatic vessel-specific VEGF receptor-3. 3 The repertoire of lymphangiogenic factors increased when it became apparent that other growth factor molecules or angiogenic factors were also regulating lymphangiogenesis. [4][5][6] As such, it has been recognized that FGF2 induces lymphangiogenesis by both direct and indirect mechanisms; it binds lymphatic endothelial cells (LECs) and stimulates their proliferation and migration in vitro 7,8 ; in addition, recent findings suggested that FGF2 reciprocally interacts with VEGF-C leading to additive lymphangiogenic activity and metastasis. 9,10 LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1), a homolog of hyaluronan receptor CD44, is expressed predominantly on lymphatic endothelium. 11 It is equally exposed to both the luminal and subluminal face of lymphatic vessel. 12 LYVE-1 cDNA encodes a 322-residue type-I integral membrane glycoprotein with a 21-residue transmembrane domain and a 63-residue cytoplasmic region. Similar to CD44, LYVE-1 has a single hyaluronan-binding domain at the N-terminus followed by a juxtamembrane region that is predicted to be heavily glycosylated. 12 LYVE-1 is also expressed in discrete populations of activated tissue macrophages and in the sinusoidal endothelium of the liver and the spleen, as well as in cancer tissues. 11,[13][14][15] LYVE-1 has been proposed to pa...
Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.
Background: PTP-PEST regulates cell migration as part of many protein complexes. Results: SKAP-Hom is a substrate of PTP-PEST that is required for proper fibroblasts migration. Enhanced migration was observed when SKAP-Hom-deficient fibroblasts are rescued with its SH3 domain mutant. Conclusion: As a novel substrate of PTP-PEST, SKAP-Hom is important in cellular migration. Significance: PTP-PEST regulates migration through a new complex involving SKAP-Hom.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.