Alterations in the phosphoproteomic profile of cells expressing a non-functional form of the SHP2 phosphatase

New Biotechnology
Salvatore CorallinoLuisa Castagnoli

Abstract

The phosphatase SHP-2 plays an essential role in growth factor signaling and mutations in its locus is the cause of congenital and acquired pathologies. Mutations of SHP-2 are known to affect the activation of the RAS pathway. Gain-of-function mutations cause the Noonan syndrome, the most common non-chromosomal congenital disorder. In order to obtain a holistic picture of the intricate regulatory mechanisms underlying SHP-2 physiology and pathology, we set out to characterize perturbations of the cell phosphorylation profile caused by an altered localization of SHP-2. To describe the proteins whose activity may be directly or indirectly modulated by SHP-2 activity, we identified tyrosine peptides that are differentially phosphorylated in wild type SHP-2 cells and isogenic cells expressing a non-functional SHP-2 variant that cannot dephosphorylate the physiological substrates due to a defect in cellular localization upon growth factor stimulation. By an iTRAQ based strategy coupled to mass spectrometry, we have identified 63 phosphorylated tyrosine residues in 53 different proteins whose phosphorylation is affected by SHP-2 activity. Some of these confirm already established regulatory mechanisms while many others suggest new po...Continue Reading

References

Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S AhmadS H Shen
Apr 1, 1997·Current Opinion in Cell Biology·B G Neel, N K Tonks
Mar 10, 1998·Cell·P HofS E Shoelson
Mar 19, 1999·Molecular and Cellular Biology·E S OhS M Thomas
Nov 11, 1999·Oncogene·H Ichijo
Feb 17, 2000·Cellular Signalling·K Ono, J Han
Mar 10, 2001·The Journal of Biological Chemistry·H ZhangS Pelech
Mar 15, 2001·Current Opinion in Cell Biology·N K Tonks, B G Neel
Jan 25, 2002·Journal of Cellular Physiology·Ratna K VadlamudiRakesh Kumar
Oct 29, 2002·Nature Cell Biology·Hiroshi HanafusaEisuke Nishida
Nov 22, 2002·American Journal of Respiratory Cell and Molecular Biology·Annette B RiceJames C Bonner
Nov 26, 2002·The Journal of Cell Biology·Asako TsubouchiHisataka Sabe
Jun 27, 2003·Trends in Biochemical Sciences·Benjamin G NeelLily Pao
Jan 14, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jannik N AndersenNiels Peter H Møller
Feb 14, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Qinghang Liu, Polly A Hofmann
Jun 1, 2004·Molecular and Cellular Biology·Maria I KontaridisAnton M Bennett
Dec 3, 2004·The Journal of Biological Chemistry·Alexandra MontagnerPatrick Raynal
Dec 17, 2005·American Journal of Human Genetics·Marco TartagliaBruce D Gelb
Dec 27, 2005·The Journal of Biological Chemistry·Maria I KontaridisBenjamin G Neel
Feb 17, 2006·Development·Lesley A JarvisRachel K Smith-Bolton
Oct 5, 2006·Current Cancer Drug Targets·David EastyD C Bennett
Oct 24, 2006·Nature Reviews. Molecular Cell Biology·Nicholas K Tonks
Jan 24, 2007·The Biochemical Journal·Tony Tiganis, Anton M Bennett
Jan 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Judit VillénSteven P Gygi
Apr 5, 2007·Nature Protocols·Shao-En Ong, Matthias Mann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

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.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.