Fetomodulin: Marker surface protein of fetal development which is modulatable by cyclic AMP

Imada, Masato; Imada, Sumi; Iwasaki, H.; Kume, Akinori; Yamaguchi, Harumi; Moore, Emma

doi:10.1016/0012-1606(87)90312-5

Cited by 64 publications

(34 citation statements)

References 18 publications

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“…Thrombomodulin is identical to the murine differentiation antigen fetomodulin, which may function in cellular differentiation during embryonic de-1850 Raife et al u velopment ( 14). In mouse embryos, this antigen is expressed by both vascular and nonvascular cells ( 14,38 ). The extracellular sequence of thrombomodulin contains an amino-terminal domain that is homologous to the lectin-like domains of many cell adhesion molecules (2).…”

Section: Discussionmentioning

confidence: 99%

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Raife¹,

Lager²,

Madison³

et al. 1994

J. Clin. Invest.

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Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities ofthrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.

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Section: Discussionmentioning

confidence: 99%

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Raife¹,

Lager²,

Madison³

et al. 1994

J. Clin. Invest.

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“…Natural anticoagulants, e.g. thrombomodulin and tissue-type plasminogen activator, are expressed high level at this interface between fetal and maternal tissue which indicates the need to counter the activation of maternally derived coagulation pro-tease in proximity to the embryo (15)(16)(17) or implies that these anticoagulant mechanism have other biologic function at this site (18). It has been reported that heparan sulfate isolated from murine Reichert's membrane bound almost quantitatively and with high affinity to AT (19).…”

mentioning

confidence: 99%

“…All the evidence above suggest that parietal endoderm would be an ideal system for anticoagulant heparan sulfate biosynthesis studies. Upon RACT treatment, F9 mouse embryonal carcinoma cells differentiate into parietal endoderm and turn on the biosynthesis of both thrombomodulin and tissue-type plasminogen activator (15)(16)(17). We reasoned that the biosynthesis of the natural anticoagulant HS act might also be dramatically elevated in RACT F9 cells.…”

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confidence: 99%

The Retinoic Acid and cAMP-dependent Up-regulation of 3-O-Sulfotransferase-1 Leads to a Dramatic Augmentation of Anticoagulantly Active Heparan Sulfate Biosynthesis in F9 Embryonal Carcinoma Cells

Zhang

Schwartz

Miller

et al. 1998

Journal of Biological Chemistry

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“…The first step of differentiation is accompanied by morphological changes and disappearance of the stage-specific embryonic antigen (SSEA-1) (3) and appearance of differentiation markers like tissue plasminogen activator (tPA) (1), laminin (2), and TROMA-1 (4,5). The second step of differentiation is accompanied by morphological changes as well and is characterized by the appearance of thrombomodulin (6,7), while expression of proteins like tPA and laminin is strongly elevated (2).…”

mentioning

confidence: 99%

The Ras/Erk Pathway Induces Primitive Endoderm but Prevents Parietal Endoderm Differentiation of F9 Embryonal Carcinoma Cells

Verheijen

Wolthuis

Bos

et al. 1999

Journal of Biological Chemistry

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The formation of parietal endoderm (PE) is one of the first differentiation processes during mouse development and can be studied in vitro using F9 embryonal carcinoma (EC) cells. Treatment of F9 EC cells with retinoic acid (RA) induces differentiation toward primitive endoderm (PrE), while differentiation toward PE is induced by subsequent addition of parathyroid hormone (PTH) or PTH-related peptide (PTHrP). The signal transduction mechanisms involved in this two-step process are largely unclear.We show that the RA-induced differentiation toward PrE is accompanied by a sustained increase in Ras activity and that ectopic expression of oncogenic Ha-Ras is sufficient to induce PrE differentiation. Ras activity subsequently decreases upon PTH-induced differentiation toward PE. This is a necessary event, since expression of oncogenic Ha-Ras in PrE-like cells prevents PTHinduced PE differentiation. Expression of active PKA in PrE-like F9 cells mimics PTH-induced PE differentiation and is again prevented by oncogenic Ha-Ras. The effect of oncogenic Ras on both differentiation steps is abolished by the MEK inhibitor PD98059 and can be mimicked by constitutively active forms of Raf and MEK.In conclusion, our data suggest that activation of the Ras/Erk is sufficient to induce differentiation to PrE and to prevent subsequent differentiation toward PE. Activation of PKA down-regulates Ras activity, resulting in disappearance of this blockade and transmission of signal(s) triggering PE differentiation.

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Fetomodulin: Marker surface protein of fetal development which is modulatable by cyclic AMP

Cited by 64 publications

References 18 publications

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

The Retinoic Acid and cAMP-dependent Up-regulation of 3-O-Sulfotransferase-1 Leads to a Dramatic Augmentation of Anticoagulantly Active Heparan Sulfate Biosynthesis in F9 Embryonal Carcinoma Cells

The Ras/Erk Pathway Induces Primitive Endoderm but Prevents Parietal Endoderm Differentiation of F9 Embryonal Carcinoma Cells

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