Biology of the TAM Receptors

Lemke, Greg

doi:10.1101/cshperspect.a009076

Cited by 491 publications

(613 citation statements)

References 169 publications

(243 reference statements)

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“…Gas6 is a member of the vitamin K-dependent protein family and interacts with receptor tyrosine kinases of the TAM (Tyro3, Axl, Mer) family (Claudio Schneider et al 1988;Lemke 2013). Gas6 has the highest affinity for Axl among TAM receptors and is often called Gas6/Axl pathway.…”

Section: Introductionmentioning

confidence: 99%

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Chen

Zhao

Jin

et al. 2016

AGE

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Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl-and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin IIinduced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin IIinduced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, AxlFc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/ FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.

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Section: Introductionmentioning

confidence: 99%

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Chen

Zhao

Jin

et al. 2016

AGE

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“…Similar considerations may also be valid for small natural molecules, such as curcumin, cinnamaldehyde and sulforaphane, which have been reported to mediate the anti-TLR4 dimerization effects, as well as for resveratrol and some flavonoids (such as EGCG, lutelolin, quercetin, chrysin, and eriodictyol), that have been reported to inhibit TBK1 kinase activity (a downstream TLR4 signaling kinase), resulting in a decreased IRF3 activation, a TLR4 signaling adaptator, and target gene expression [101][102][103][104]150] (see Table 5). …”

Section: Therapeutic Role Of Tlr-4 Pathway: From Experimental Data Tomentioning

confidence: 99%

“…They are involved in inhibiting an over-or unnecessary activation of TLR-4 pathway, as well as other PRRs. In Table 4, many of these molecules are listed and described [101][102][103][104].…”

Section: The Role Of Tlr-4 In the Maintenance Of Aorta Homeostasismentioning

confidence: 99%

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

Balistreri

Ruvolo

Lio

et al. 2017

Journal of Molecular and Cellular Cardiology

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“…This includes tissue factor (TF), thrombin receptor (PAR-1) along with other protease activated receptors (PARs), urokinase receptor (uPAR), thrombomodulin (TM), endothelial protein C receptor (EPCR), receptors for protein S (TAM group), integrins, and growth factor receptors that can be transactivated by the coagulation system [10][11][12][13][14]. These molecular interactions activate intracellular signalling pathways and change the expression of several genes [15,16], including mediators of angiogenesis, inflammation and other processes relevant to cancer [10,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Oncogenes and the coagulation system – forces that modulate dormant and aggressive states in cancer

Magnus

D’Asti

Meehan

et al. 2014

Thrombosis Research

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Biology of the TAM Receptors

Cited by 491 publications

References 169 publications

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

Oncogenes and the coagulation system – forces that modulate dormant and aggressive states in cancer

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