Adrenomedullin stimulates DNA synthesis and cell proliferation via elevation of cAMP in Swiss 3T3 cells

FEBS Letters

Seufferlein, Thomas¹  Smith, David M.²  Bloom, Stephen R.²  Coppock, Hedley A.²  Rozengurt, Enrique¹  Withers, Dominic J.¹ 

[1] Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK;Division of Endocrinology, Department of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

关键词: Neuropeptide;    Signal transduction;    Growth control;    CGRP;    calcitonin-gene related peptide;    PKC;    protein kinase C;    FAK;    focal adhesion kinase;    DMEM;    Dulbecco's modified Eagle's medium;    FBS;    fetal bovine serum;    PDB;    phorbol 12;    13-dibutyrate;    IBMX;    3-isobutyl-l-methylxanthine;    EGF;    epidermal growth factor;    MARCKS;    myristoylated;    alanine-rich C kinase substrate;    PKA;    protein kinase A;    VSM;    vascular smooth muscle;    BAE;    bovine aortic endothelial;    Tyr (P) tyrosine phosphate;    BrDu;    bromodeoxyuridine;    mAb;    monoclonal antibody;    RIA;    radioimmunoassay;   

DOI  :  10.1016/0014-5793(95)01427-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Our results demonstrate that the novel vasoactive regulatory peptide adrenomedullin is a potent mitogen for Swiss 3T3 cells. Acting via a specific adrenomedullin receptor, it stimulates a dose-dependent increase in DNA synthesis in synergy with insulin. Additionally, adrenomedullin stimulates further progression through the cell cycle resulting in cell proliferation, an effect that was further enhanced by the presence of insulin. Adrenomedullin rapidly induces accumulation of intracellular CAMP but does not stimulate an increase in intracellular Ca²⁺, activation of protein kinase C, or tyrosine phosphorylation of intracellular substrates. Adrenomedullin-stimulated mitogenesis is markedly enhanced in Swiss 3T3 cells stably transfected with a constitutively activated Gsα, which are highly sensitive to agents that elevate cAMP, and is inhibited by the PKA inhibitor H-89. Adrenomedullin is, thus, identified as a novel mitogenic regulatory peptide acting via cAMP.

【 授权许可】

Unknown