Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2

The EMBO Journal
T M SaxtonT Pawson

Abstract

Shp-1, Shp-2 and corkscrew comprise a small family of cytoplasmic tyrosine phosphatases that possess two tandem SH2 domains. To investigate the biological functions of Shp-2, a targeted mutation has been introduced into the murine Shp-2 gene, which results in an internal deletion of residues 46-110 in the N-terminal SH2 domain. Shp-2 is required for embryonic development, as mice homozygous for the mutant allele die in utero at mid-gestation. The Shp-2 mutant embryos fail to gastrulate properly as evidenced by defects in the node, notochord and posterior elongation. Biochemical analysis of mutant cells indicates that Shp-2 can function as either a positive or negative regulator of MAP kinase activation, depending on the specific receptor pathway stimulated. In particular, Shp-2 is required for full and sustained activation of the MAP kinase pathway following stimulation with fibroblast growth factor (FGF), raising the possibility that the phenotype of Shp-2 mutant embryos results from a defect in FGF-receptor signalling. Thus, Shp-2 modulates tyrosine kinase signalling in vivo and is crucial for gastrulation during mammalian development.

References

Dec 11, 1992·Proceedings of the National Academy of Sciences of the United States of America·R M FreemanB G Neel
Feb 17, 1995·The Journal of Biological Chemistry·S PluskeyS E Shoelson
Feb 16, 1995·Nature·T Pawson
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S AhmadS H Shen
Jun 18, 1993·Cell·J A Cooper, B Howell
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A KazlauskasM Valius
Jan 27, 1995·Cell·G B CohenD Baltimore
Nov 1, 1994·Trends in Biochemical Sciences·H Sun, N K Tonks
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·A M BennettB G Neel
Aug 1, 1993·Current Opinion in Genetics & Development·R S Beddington, J C Smith
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A NagyJ C Roder
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·D PeiC T Walsh
Mar 1, 1996·Molecular and Cellular Biology·A M BennettB G Neel

❮ Previous
Next ❯

Citations

Jan 20, 2007·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Sayo KawaiNobuyuki Hamajima
Aug 8, 2012·Frontiers of Medicine·Shuangwei LiGen-Sheng Feng
Apr 2, 2008·Current Oncology Reports·Taolin Yi, Daniel Lindner
Sep 7, 2000·Biochemical Pharmacology·B P Kennedy, C Ramachandran
Sep 27, 2003·Developmental Biology·Elizabeth A CarrollJohn Klingensmith
Mar 10, 1998·Cell·P HofS E Shoelson
Jan 29, 2002·Cellular Signalling·Helen WheadonMelanie J Welham
Jul 23, 1999·Mechanisms of Development·J den Hertog
Mar 15, 2001·Current Opinion in Cell Biology·N K Tonks, B G Neel
Oct 2, 2003·Current Opinion in Cell Biology·Kris A DeMaliKeith Burridge
Apr 30, 1998·Current Opinion in Cell Biology·D Van Vactor
Apr 19, 2008·Cell Death and Differentiation·X-D Zhou, Y M Agazie
Oct 29, 2009·Nature Genetics·Santhi K GaneshJing-Ping Lin
Feb 22, 2002·European Journal of Biochemistry·Alan ChengMichel L Tremblay
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Katja S GrossmannCarmen Birchmeier
Jan 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hsiao-Hui LeeShu Chien
Sep 16, 2010·The Journal of Biological Chemistry·Kosuke MatsuoFawaz G Haj
Jun 10, 2006·The Journal of Biological Chemistry·Ning WangZhizhuang Joe Zhao
Mar 6, 2009·The Journal of Biological Chemistry·Xiangdong Zhou, Yehenew M Agazie
Sep 28, 2002·Current Opinion in Pediatrics·Ellen Dees, H Scott Baldwin
Dec 17, 2003·Current Opinion in Hematology·Marco TartagliaMignon L Loh
Apr 17, 2012·Current Opinion in Hematology·Sarah C Nabinger, Rebecca J Chan
Nov 1, 2001·Science's STKE : Signal Transduction Knowledge Environment·M Goldfarb
Nov 7, 2012·Molecular and Cellular Biology·Fatih MercanAnton M Bennett
Jun 2, 2006·Molecular and Cellular Biology·Emilie A Bard-ChapeauGen-Sheng Feng
Mar 14, 2012·Molecular and Cellular Biology·Aurelio Pio NardozzaLuisa Castagnoli
Dec 14, 1999·Molecular and Cellular Biology·A M O'ReillyB G Neel

❮ 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.