"Shping 2" different cellular localizations - a potential new player in aging processes.
The functions of the ubiquitously expressed protein tyrosine phosphatase Shp-2 are dependent on its localization. Cytosolic Shp-2 is known to modulate different pathways involved in cell growth, cell development, tissue inflammation and cellular chemotaxis. But Shp-2 is also localized in the nucleus and the mitochondria. Nuclear Shp-2 forms a complex with the signal transducer and activator of transcription 5 (STAT5) which then binds to DNA and regulates transcription of milk genes. In contrast, nuclear Shp-2 dephosphorylates STAT1 and thereby inhibits gene transcription. In addition, it counteracts the oxidative stress dependent nuclear export of Telomerase Reverse Transcriptase (TERT) mediated by members of the Src kinase family, a process leading to replicative senescence. For the recently found mitochondrial Shp-2 an involvement in the regulation of the cellular redox balance is discussed. Shp-2 shows the ability to regulate reactive oxygen species formation in the mitochondria. There are hints that mitochondrial Shp-2 and Src are involved in the regulation of respiratory chain activity. Since a substantial fraction of TERT has been found in the mitochondria, it is hypothesized that mitochondrial Shp-2 acts as a positive regulator of TERT in the mitochondria, similar to its nuclear role. Taken together, Shp-2 seems to be a new player in aging processes.
Department of Molecular Cell & Aging Research, IUF at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany.
Sascha
S
Jakob
Joachim
J
Altschmied
Judith
J
Haendeler
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008894:Milk Proteins / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism
D008894:Milk Proteins; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D020794:Receptor Protein-Tyrosine Kinases; D019098:Telomerase; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11