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Selective interaction of MRAP proteins with somatostatin receptors in the Mus musculus
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  • Meng Wang,
  • Jing Xu,
  • Xiaowei Lei,
  • Cong Zhang,
  • Shangyun Liu,
  • Kuang Zhe,
  • Yanbin Fu,
  • Shen Qu,
  • Qingfen Li,
  • Chao Zhang
Meng Wang
Tongji University Tenth People's Hospital
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Jing Xu
Tongji University Tenth People's Hospital
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Xiaowei Lei
Tongji University Tenth People's Hospital
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Cong Zhang
Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital
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Shangyun Liu
Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital
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Kuang Zhe
Tongji University Tenth People's Hospital
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Yanbin Fu
Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital
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Shen Qu
Tongji University Tenth People's Hospital
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Qingfen Li
Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital
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Chao Zhang
Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital

Corresponding Author:[email protected]

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Abstract

Somatostatin (SST) receptors are well known to regulate exocrine secretions, neurotransmission and inhibit cell proliferation. SSTR subtypes exhibit heterodimerization with unique signaling characteristics. In the present study, using western blot and co-immunoprecipitation, FACS analysis, immunofluorescence, we investigated the differential interaction between MRAP1 and SSTRs and the role of MRAP1 on mouse SSTR2/SSTR3 and SSTR2/SSTR5 heterodimerization in HEK293 cells. The interaction binding sites of SSTR2/SSTR3 or SSTR2/SSTR5 with MRAP1 depend on SSTR3 and SSTR5 but not SSTR2. MRAP1 binding sites on SSTR3 are extensive, while the binding sites on SSTR5 are concentrated on TM6 and TM7. We also determined that MRAP1 enhanced agonist-mediated cAMP inhibition by inhibiting SSTR2/SSTR3 and SSTR2/SSTR5 heterodimerization. Up-regulation of ERK1/2 phosphorylation, p27Kip1 and increased cell growth inhibition when co-expressing SSTR2/SSTR3 or SSTR2/SSTR5 with MRAP1, suggested an effect of MRAP1 on anti-proliferative response of two SSTR heterodimers. Taken together, these results provide new insights for binding protein MRAP1 in the maintenance and regulation of mouse SSTR dimers which might be helpful to better understand the molecular mechanism involving SSTRs in tumor biology.