Annexin V inhibits the 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of Shc in MCF-7 cells

Sato, Hírokazu; Ogata, Hideaki; Luca, Luigi M. De

doi:10.1038/sj.onc.1203615

Cited by 33 publications

(19 citation statements)

References 55 publications

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“…However, other groups (40) have shown that stimulation of PKC in COS cells led to activation of Ras and formation of Ras-Raf-1 complexes that activate Raf-1. Sato et al (56) also reported that TPA induces activation of Ras and ERK in MCF-7 cells. Consequently, we conclude that PKC is an upstream component of the Ras/MAPK signaling pathway in primary BMC cultures.…”

Section: Discussionmentioning

confidence: 95%

Parathyroid Hormone-related Peptide Stimulates Osteogenic Cell Proliferation through Protein Kinase C Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway

Miao

Tong²,

Chan³

et al. 2001

Journal of Biological Chemistry

107

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We investigated the mechanisms of parathyroid hormone-related peptide (PTHrP)-mediated effects on osteogenic cells in primary rat bone marrow cell (BMC) cultures. We first demonstrated by reverse transcriptase-polymerase chain reaction and immunocytochemistry that BMCs express the type I parathyroid hormone/PTHrP receptor. Treatment with PTHrP increased osteogenic cell proliferation as determined by [ 3 H]thymidine and bromodeoxyuridine incorporation and augmented osteogenic colonies. Immunocytochemistry and Western blotting revealed no direct effect on expression of the osteoblast markers, type I collagen, bone sialoprotein, and osteocalcin, indicating that PTHrP did not directly stimulate differentiation in this system. PTHrP increased mitogen-activated protein kinase (MAPK) activity in BMC and MAPK activity, and PTHrP-induced osteogenic cell proliferation could be blocked by the MEK inhibitor PD-098059. PTHrP also increased Ras activity in BMC. Although wortmannin and H8, inhibitors of phosphoinositol 3-kinase and protein kinase A, respectively, did not block PTHrP-stimulated Ras or MAPK activity, chelerythrin chloride, a known protein kinase C inhibitor, did block these PTHrP actions as well as PTHrP-induced osteogenic cell proliferation. These results demonstrate that PTHrP stimulates osteogenic cell proliferation in rat marrow mesenchymal progenitor cells through protein kinase C-dependent activation of the Ras and MAPK signaling pathway.Parathyroid hormone-related peptide (PTHrP) 1 was initially discovered as the pathogenetic mediator of malignancy-associated hypercalcemia (MAH). Originally, PTHrP was considered to be a skeletal catabolic agent as patients with MAH develop marked osteoclastic bone resorption. However, as is the case with PTH in hyperparathyroidism, this catabolic skeletal effect of PTHrP in MAH occurs in the context of continuous exposure of the skeleton to PTHrP. In contrast, administration of PTH to rodents on an intermittent basis increases bone mass. This anabolic effect of intermittent PTH administration in osteoporosis has been extensively explored (1). Several groups have also demonstrated that intermittent PTHrP administration increases bone mass in rats in vivo (2-8), and in humans, a 2-week course of PTHrP has been associated with activation of bone formation and suppression of bone resorption in postmenopausal women (9). Analogs of PTHrP have been developed in an attempt to improve its anabolic efficacy. One such analog, RS-66271, has received attention because of its pronounced bone anabolic activity when given intermittently to ovariectomized, osteopenic rats (10). A rapid increase in the number of osteoblasts on trabecular surfaces was observed following initiation of treatment (11). Additional evidence in support of an anabolic effect of PTHrP on bone comes from studies of heterozygous PTHrP "knockout" animals that exhibit haploinsufficiency and evidence of reduced trabecular bone volume (12). Despite these observations the cellular basis for the anabolic actions of PTHrP i...

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Section: Discussionmentioning

confidence: 95%

Parathyroid Hormone-related Peptide Stimulates Osteogenic Cell Proliferation through Protein Kinase C Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway

Miao

Tong²,

Chan³

et al. 2001

Journal of Biological Chemistry

107

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“…In general, annexins have been implicated in the maintenance of calcium homeostasis, signal transduction, receptor-mediated endocytosis, cell proliferation and growth, ion channel formation, and the secretion of neurotransmitters and hormones (34,35). AxV, in particular, has been implicated in regulating cell proliferation (36) and as a protein kinase C inhibitor (37,38).…”

Section: Discussionmentioning

confidence: 99%

Annexin V Associates with the IFN-γ Receptor and Regulates IFN-γ Signaling

León

Nandan

López

et al. 2006

The Journal of Immunology

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Many of the biological activities of IFN-γ are mediated through the IFN-γR3-linked Jak-Stat1α pathway. However, regulation of IFN-γ signaling is not fully understood, and not all responses to IFN-γ are Stat1α dependent. To identify novel elements involved in IFN-γ cell regulation, the cytoplasmic domain of the R2 subunit of the human IFN-γR was used as bait in a yeast two-hybrid screen of a human monocyte cDNA library. This identified annexin A5 (AxV) as a putative IFN-γR binding protein. The interaction was confirmed in pull-down experiments in which a GST-R2 cytoplasmic domain fusion protein was incubated with macrophage lysates. Furthermore, immunoprecipitation using anti-IFN-γR2 Abs showed that AxV interacted with IFN-γR2 to form a stable complex following incubation of cells with IFN-γ. In 293T cells with reduced expression of AxV, brought about by small interfering RNA targeting, activation of Jak2 and Stat1α in response to IFN-γ was enhanced. Inhibition of cell proliferation, a hallmark of the IFN-γ response, also was potentiated in HeLa cells treated with small interfering RNA directed at AxV. Taken together, these results suggest that through an inducible association with the R2 subunit of the IFN-γR, AxV modulates cellular responses to IFN-γ by modulating signaling through the Jak-Stat1 pathway.

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“…A PMA-stimulated externalization of anxA5 from alveolar type II cells has been previously shown by Sohma et al (47). In our case, THP-1 cells might be releasing anxA5 during PMA stimulation as a self-defense mechanism for it has been shown that anxA5 may inhibit phorbol ester-activated pathways (48). Other stress situations have been described that cause a change in anxA5 localization.…”

Section: Discussionmentioning

confidence: 99%

Annexin A5 Down-regulates Surface Expression of Tissue Factor

Ravassa

Bennaghmouch

Kenis

et al. 2005

Journal of Biological Chemistry

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Phosphatidylserine (PtdSer) is exposed on the external leaflet of the plasma membrane during apoptosis. The protein annexin A5 (anxA5) shows high affinity for PtdSer. When anxA5 binds to the PtdSer-expressing membranes during apoptosis, it crystallizes as an extended two-dimensional network and activates thereby a novel portal of cell entry that results in the internalization of the PtdSer-expressing membrane patches. This novel pathway of cell entry is potentially involved in the regulation of the surface expression of membrane receptors. In this study we report the regulation of surface expression of the initiator of blood coagulation tissue factor (TF) by this novel pathway of cell entry. AnxA5 induces the internalization of tissue factor expressed on the surface of apoptotic THP-1 macrophages. This down-regulation depends on the abilities of anxA5 to bind to PtdSer and to form a two-dimensional crystal at the membrane. We furthermore show that THP-1 cells produce and externalize anxA5 that cause the internalization of TF in an autocrine type of mechanism. We extended our in vitro work to the in vivo situation and show in a mouse model that anxA5 causes the downregulation of TF expression by smooth muscle cells of the media of the carotid artery that was mechanically injured. In conclusion, anxA5 down-regulates surfaceexpressed TF by activating the novel portal of cell entry. This mechanism may be part of a more general autocrine function of anxA5 to regulate the plasma membrane receptor repertoir under stress conditions associated with the surface expression of PtdSer.

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Annexin V inhibits the 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of Shc in MCF-7 cells

Cited by 33 publications

References 55 publications

Parathyroid Hormone-related Peptide Stimulates Osteogenic Cell Proliferation through Protein Kinase C Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway

Parathyroid Hormone-related Peptide Stimulates Osteogenic Cell Proliferation through Protein Kinase C Activation of the Ras/Mitogen-activated Protein Kinase Signaling Pathway

Annexin V Associates with the IFN-γ Receptor and Regulates IFN-γ Signaling

Annexin A5 Down-regulates Surface Expression of Tissue Factor

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