Structure-function and biological role of betacellulin

Dunbar, Andrew; Goddard, C.

doi:10.1016/s1357-2725(00)00028-5

Cited by 112 publications

(111 citation statements)

References 63 publications

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“…In contrast, immunolocalization of ErbB-4 in term placentas is predominantly observed in EVTs. In the current study, the binding affinity to BTC of ErbB-1 homodimers is comparable to that of ErbB-4 homodimers (13). Furthermore, recent study has shown that appropriate biological responsiveness to ErbB ligands is determined by the levels of expression of specific ErbB receptor combinations (37).…”

Section: Discussionsupporting

confidence: 57%

“…Indeed, recent investigation regarding HB-EGF has shown that the biological effects of the transmembrane form on human luteinized granulosa cells are different from those of the soluble form (41). Similar to other members of the EGF family, BTC is synthesized as a transmembrane precursor, which is subject to proteolytic cleavage of its ectodomain to produce a soluble mature growth factor (13). In the present study, we demonstrated the expression of the soluble form of BTC protein with western immunoblot analysis using a polyclonal antibody raised against human recombinant BTC.…”

Section: Discussionmentioning

confidence: 99%

“…The EGF family, consisting of at least 15 members (12), is characterized by a six-cysteine consensus motif and forms three intramolecular disulfide bonds (13). These proteins are initially synthesized as transmembrane precursor peptides that are secreted by proteolytic cleavage of the extracellular domain and bind to erbB tyrosine kinase receptors (ErbB-1, ErbB-2, ErbB-3 and ErbB-4) as either membrane-anchored precursor peptides or soluble mature hormones.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

Tanimura

Nakago²,

Murakoshi³

et al. 2004

European Journal of Endocrinology

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Objective: Betacellulin (BTC), purified and cloned from mouse beta cell tumor (BTC-JC10), is regarded as a new member of the epidermal growth factor family. The present study was conducted to clarify the expression of BTC and its receptors, ErbB-1 and ErbB-4, in the trophoblasts in the human placenta over the course of pregnancy. Design and Methods: Human placental tissues were obtained from 4 pregnant women at the 4th to 5th week of pregnancy (very early placentas), 10 women at the 6th to 12th week (early placentas), 5 women at the 18th to 21st week (mid placentas) and 8 women at the 38th and 40th week (term placentas). The mRNA expressions of BTC, erbB-1 and erbB-4 were evaluated by quantitative RT-PCR with Southern blotting and the expression of the soluble form of BTC was determined by western immunoblot with a specific antibody to BTC protein. Immunohistochemical staining of BTC, ErbB-1 and ErbB-4 was also performed. Results: The levels of BTC mRNA expression in early and mid placentas were significantly higher than those in term placentas. The soluble form of BTC protein with an estimated molecular mass of 9.5 kDa was expressed in early and mid placentas, whereas the soluble form was not detected in term placentas. BTC from very early placentas until mid placentas was immunolocalized in syncytiotrophoblasts (S-cells), and was most abundant in early placentas. In contrast, BTC was immunolocalized in extravillous trophoblasts (EVTs), but not in villous trophoblasts in term placentas. The levels of erbB-1 mRNA in the early and mid placentas were significantly higher than those in term placentas, whereas the levels of erbB-4 mRNA in early placentas were significantly lower than those in mid and term placentas. ErbB-1 was immunolocalized in cytotrophoblasts in very early placentas, whereas it was immunolocalized in S-cells from early until term placentas. ErbB-4 from very early placentas until mid placentas was immunolocalized in S-cells, whereas ErbB-4 in the term placentas was detected in EVTs, but not in villous trophoblasts. Conclusions: These findings provide evidence for changes in expression and cytological localization of BTC and its receptors in the trophoblasts in human placenta over the course of pregnancy. BTC may play a pivotal role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through the maintenance of EVT cell function via ErbB-4 in term placentas.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

Tanimura

Nakago²,

Murakoshi³

et al. 2004

European Journal of Endocrinology

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“…Many peptide ligands of ErbB receptors have been identified, including epidermal growth factor (EGF), heparin-binding EGF-like growth factor (HB-EGF), TGF-␣, amphiregulin, epiregulin, ␤-cellulin, and neuregulin 1-4. All of these ligands contain one or more of the conserved EGF motif (CX 7 CX 4 -5 CX 10 -13 CXCX 8 GXRC, where X represents any amino acid) (7,8), but they differ in receptor specificity (9). Moreover, all ligands are synthesized as transmembrane precursors and are released by ectodomain shedding via proteolysis (10).…”

Section: Epidermal Growth Factor Receptor (Egfr)mentioning

confidence: 99%

Prolidase Directly Binds and Activates Epidermal Growth Factor Receptor and Stimulates Downstream Signaling

Yang

Ding

et al. 2013

Journal of Biological Chemistry

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Background: All known ligands of EGF receptor (EGFR) are characterized by the EGF motif and generated from transmembrane precursors. Results: Prolidase, a cytosolic dipeptidase devoid of EGF motif, binds and activates EGFR independent of its dipeptidase activity when present outside of cell. Conclusion: Prolidase is a novel EGFR ligand.Significance: This shows a new function of prolidase and new mechanism of EGFR activation.

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“…Betacellulin binds to both ErbB-1 and ErbB-4, but not ErbB-3, and EGF binds only to ErbB-1 (Riese and Stern, 1998;Dunbar and Goddard, 2000). The results shown in Figure 2 demonstrate that betacellulin is as e ective as heregulin in promoting ErbB-2 translocation.…”

mentioning

confidence: 89%

Heregulin-dependent translocation and hyperphosphorylation of ErbB-2

Zhou

Carpenter

2001

Oncogene

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Previous data have shown that in several tumor cells lines the addition of heregulin results in the translocation of ErbB-4 to a detergent-insoluble membrane fraction where it is hypertyrosine phosphorylated. The data herein demonstrate that heregulin or betacellulin, but not EGF, promotes the rapid translocation of ErbB-2, the heterodimerization partner for ErbB-4, to the same detergent-insoluble fraction in T47 D mammary carcinoma cells. The translocation of ErbB-2 and ErbB-4, but not ErbB-3, to this detergent-insoluble fraction is readily detected 2 min after the addition of heregulin. ErbB-2 present in this detergent-insoluble membrane fraction is tyrosine phosphorylated to a level fourfold greater than the majority of cellular ErbB-2 present in the detergentsoluble membrane fraction. These results suggest the ligand-dependent formation of hyperphosphorylated ErbB-4/ErbB-2 dimers coordinate with translocation to a putative membrane microdomain. Oncogene (2001) 20, 3918 ± 3920.

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Structure-function and biological role of betacellulin

Cited by 112 publications

References 63 publications

Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

Prolidase Directly Binds and Activates Epidermal Growth Factor Receptor and Stimulates Downstream Signaling

Heregulin-dependent translocation and hyperphosphorylation of ErbB-2

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