title: Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells.
abstract: We previously reported that bone morphogenetic proteins (BMPs), members of the transforming growth factor superfamily, together with the basement membrane glycoprotein laminin-1 (Ln-1), promote proliferation of fetal pancreatic cells and formation of colonies containing peripheral insulin-positive cells. Here, we further investigate the cross-talk between BMP and Ln-1 signals. By RT-PCR, receptors for BMP (BMPR) (excepting BMPR-1B) and Ln-1 were expressed in the fetal pancreas between E13.5 and E17.5. Specific blocking antibodies to BMP-4 and -6 and selective BMP antagonists partially inhibited colony formation by fetal pancreas cells. Colony formation induced by BMP-6 and Ln-1 was completely abolished in a dose-dependent manner by blocking Ln-1 binding to its alpha(6) integrin and alpha-dystroglycan receptors or by blocking the Ln-1 signaling molecules, phosphatidyl-inositol-3-kinase (P13K) and MAP kinase kinase-1. These results demonstrate a convergence of BMP and Ln-1 signaling through P13K and MAP kinase pathways to induce proliferation and colony formation in E15.5 fetal mouse pancreatic cells.
authors.affiliation: Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Australia. jiang@wehi.edu.au
authors.forename: Fang-Xu
authors.initials: FX
authors.lastname: Jiang
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005333:Fetus; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D017474:Receptors, Laminin / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D007797:Laminin; D017978:Receptors, Growth Factor; D017474:Receptors, Laminin; C121346:laminin 1; D017346:Protein Serine-Threonine Kinases; C498219:Bmpr2 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II