Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells.
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.
Jiang
Fang-Xu
FX
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Australia. jiang@wehi.edu.au
Harrison
Leonard C
LC
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*
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