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.
(1) Department of Pediatric Oncology,
Dana-Farber Cancer Institute, Massachusetts
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]