PubMed Journals: J Biol Chem

  Source:		PMID: 10617656

    		J Biol Chem. 2000 Jan 7;275(1):599-604.
			Cytosolic tyrosine dephosphorylation of
			STAT5. Potential role of SHP-2 in STAT5 regulation.

			Yu CL(1), Jin YJ, Burakoff SJ.

			Author Information
			(1) Department of Pediatric Oncology,
			Dana-Farber Cancer Institute, Massachusetts
			02115, USA.

			STAT5, a member of the signal transducers and
			activators of transcription (STATs), is
			important in modulating T cell functions
			through interleukin-2 (IL-2) receptors.
			Like other STAT proteins, STAT5 undergoes
			a rapid activation and inactivation cycle
			upon cytokine stimulation. Tyrosine phosphorylation
			and dephosphorylation are critical in regulating
			STAT5 activity. A number of protein tyrosine
			kinases have been shown to phosphorylate
			STAT5; however, the phosphatases responsible
			for STAT5 dephosphorylation remain unidentified.
			Using CTLL-20 as a model system, we provide
			evidence that tyrosine dephosphorylation
			of STAT5 subsequent to IL-2-induced phosphorylation
			occurs in the absence of STAT5 nuclear translocation
			and new protein synthesis. Nevertheless, down-regulation
			of the upstream Janus kinase activity during
			the deactivation cycle of IL-2-induced signaling
			does involve new protein synthesis. These
			findings point to the constitutive presence
			of STAT5 tyrosine phosphatase activity in
			the cytosolic compartment. We further demonstrate
			that SHP-2, but not SHP-1, directly dephosphorylates
			STAT5 in an in vitro tyrosine phosphatase
			assay with purified proteins. Furthermore,
			tyrosine-phosphorylated STAT5 associates
			with the substrate-trapping mutant (Cys
			--> Ser) of SHP-2 but not SHP-1. These results
			suggest a potential role for cytoplasmic
			protein-tyrosine phosphatases in directly
			dephosphorylating STAT proteins and in maintaining
			a basal steady state level of STAT activity.

			PMID: 10617656 [Indexed for MEDLINE]

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