Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SHP-1 (also known as PTP1C, SHPTP-1, SHP, and HCP) is an SH2 domain-containing protein-tyrosine phosphatase. We have stably overexpressed the native form and a catalytically inactive cysteine to serine mutant of the enzyme, SHP-1-(Cys --> Ser), in human cervical carcinoma HeLa cells. Following stimulation of the cells with epidermal growth factor (EGF) and interferon-gamma (INF-gamma), signal transducers and activators of transcription (STAT) activity was analyzed by using two 32P-labeled DNA probes, namely hSIE which is derived from a high affinity mutant form of the serum-inducible element in the c-fos promotor and GAS which resembles the INF-gamma activation site. EGF induced hSIE binding activity only, and the activity was suppressed by approximately 70% when the inactive mutant form of SHP-1 was expressed but was essentially unaffected by expression of the native enzyme. INF-gamma treatment resulted in appearance of both hSIE and GAS binding activities. While expression of the inactive mutant reduced the activities by 30-50%, the native enzyme caused a 20-30% increase. Consistent with effects on STAT activation, altered SHP-1 expression also affected EGF-induced activation of the mitogen-activated protein kinase pathway; expression of SHP-1-(Cys --> Ser) inhibited activity of MEK by approximately 25%, whereas expression of SHP-1 resulted in a approximately 25% increase. Further studies revealed that overexpression of SHP-1 caused decreased tyrosine phosphorylation of the EGF receptor and that EGF induced phosphorylation and recruitment of SHP-1. Together, the data suggest that SHP-1 is positively involved in EGF- and INF-gamma-induced STAT activation in non-hematopoietic HeLa cells and that, in the EGF signaling system, SHP-1 functions at least partly by modulating tyrosine phosphorylation of EGF receptor.
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PMID:Positive effects of SH2 domain-containing tyrosine phosphatase SHP-1 on epidermal growth factor- and interferon-gamma-stimulated activation of STAT transcription factors in HeLa cells. 928 52

Interferons are essential for establishing cytotoxic T-lymphocyte immunity against viral pathogens through different mechanisms including the modulation of antigen presentation to T-cell subsets. At the present time, interferons have yet to be isolated from teleost fish. We have developed a salmonid model to examine whether MHC gene regulation is modulated during acute viral infection in trout, an event attributable to interferons in mammals. During peak infection with infectious hematopoietic necrosis virus, induction of STAT-1, PSMB9A and ABCB2 mRNA was evident in all tissues within infected fish, as compared with controls. In addition, MHC class Ia and beta(2) microglobulin (beta(2)m) transcript levels were enhanced within the experimental group but surprisingly, splenic and pronephric class IIB mRNA expression was virtually absent. A time-course study looking at 24, 72 and 192 h post-infection was then performed to determine the overall kinetics of this response. STAT-1 and PSMB9A message levels increased early during the immune response and remain at relatively high levels until the final time point. MHC class Ia expression is not consistently upregulated until midway in the response. MHC class IIB transcripts are downregulated by 72 h in the spleen and pronephros and then partially restored by 192 h. Finally, analysis of the putative promoter regions for PSMB9A and ABCB2 identified interferon (IFN) regulatory factory (IRF-1) and INF-gamma (GAS) activation sites that may be involved in the regulation of these genes during viral infection.
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PMID:Induction of the rainbow trout MHC class I pathway during acute IHNV infection. 1246 98