Induction of epithelial tubules by growth factor HGF depends on the STAT pathway

Nature
C BoccaccioP M Comoglio

Abstract

Hepatocyte growth factor (HGF) induces a three-phase response leading to the formation of branched tubular structures in epithelial cells. The HGF receptor tyrosine kinase works through a Src homology (SH2) docking site that can activate several signalling pathways. The first phase of the response (scattering), which results from cytoskeletal reorganization, loss of intercellular junctions and cell migration, is dependent on phosphatidylinositol-3-OH kinase and Rac activation. The second phase (growth) requires stimulation of the Ras-MAP kinase cascade. Here we show that the third phase (tubulogenesis) is dependent on the STAT pathway. HGF stimulates recruitment of Stat-3 to the receptor, tyrosine phosphorylation, nuclear translocation and binding to the specific promoter element SIE. Electroporation of a tyrosine-phosphorylated peptide, which interferes with both the association of STAT to the receptor and STAT dimerization, inhibits tubule formation in vitro without affecting either HGF-induced 'scattering' or growth. The same result is obtained using a specific 'decoy' oligonucleotide that prevents STAT from binding to DNA and affecting the expression of genes involved in cell-cycle regulation (c-fos and waf-1). Activation o...Continue Reading

References

May 11, 1989·Nature·S GiordanoP M Comoglio
Dec 1, 1986·Molecular and Cellular Biology·M Z GilmanR A Weinberg
Feb 16, 1995·Nature·T Pawson
Jan 1, 1995·Annual Review of Biochemistry·C Schindler, J E Darnell
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Jun 1, 1996·The Journal of Cell Biology·M SachsW Birchmeier
Jun 14, 1996·The Journal of Biological Chemistry·C PonzettoP Comoglio
Jan 15, 1997·Genes & Development·X LiuL Hennighausen
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·K TakedaS Akira

❮ Previous
Next ❯

Citations

Jul 27, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·A C OatesA F Wilks
Dec 20, 2005·Clinical and Experimental Nephrology·Shigeo Horie
Jun 30, 2005·Cancer Metastasis Reviews·Marcin KortylewskiHua Yu
Jan 5, 2008·Cancer Metastasis Reviews·Alessandra GentilePaolo M Comoglio
May 4, 2012·Archives of Pharmacal Research·Kyung Hee JungSoon-Sun Hong
Nov 30, 2011·Hormones & Cancer·Alessia LocatelliCarol A Lange
Oct 28, 1998·Trends in Cell Biology·C Birchmeier, E Gherardi
Aug 26, 2006·Nature Clinical Practice. Nephrology·Eric G Neilson
Jul 25, 2006·Nature Reviews. Cancer·Carla Boccaccio, Paolo M Comoglio
Aug 22, 2002·Nature Reviews. Cancer·Jean Paul Thiery
May 31, 2008·Nature Reviews. Drug Discovery·Paolo M ComoglioLivio Trusolino
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Livio TrusolinoPaolo M Comoglio
Feb 3, 2005·Cell Research·Chong Feng Gao, George F Vande Woude
Apr 12, 2000·Kidney International·G A VargasP M Jehle
May 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Klaus HellmuthWalter Birchmeier
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J TalbotThomas Weimbs
Mar 5, 2011·The Journal of Biological Chemistry·Thorsten JungMargot Zöller
Jan 17, 2003·Molecular Biology of the Cell·Salvador Aznar BenitahJuan Carlos Lacal
Sep 1, 2007·Molecular Biology of the Cell·Fenghua ZengRaymond C Harris
Sep 24, 2010·Molecular Biology of the Cell·Minji KimKeith E Mostov
May 9, 2001·Current Opinion in Nephrology and Hypertension·J Barasch
Mar 10, 2001·Cold Spring Harbor Symposia on Quantitative Biology·T WelteX Y Fu
Jan 26, 2002·Molecular and Cellular Biology·Markus MüllerCarola Ponzetto
May 5, 2005·Molecular and Cellular Biology·M Cristina StellaPaolo M Comoglio

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.