Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and UL138 Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways
Regulation of the epidermal growth factor (EGF) receptor (EGFR) signaling is essential for the replication of human cytomegalovirus (HCMV) and the latency and reactivation in CD34 + hematopoietic progenitor cells. HCMV microRNAs (miRNAs) provide a means to modulate the signal is activated by EGF through targeting EGFR signaling pathway components. Here, we show that miR-US5-2 HCMV immediate critical downregulates EGFR GAB1 adapter proteins that mediate sustained activation and signals through phosphatidylinositol 3-kinase (PI3K) and MEK / extracellular signal-regulated kinase (ERK) pathway and cell proliferation in response to EGF.
UL138 HCMV expression is regulated by the transcription factor early growth response gene 1 (EGR1) downstream of EGFR-induced MEK / ERK signaling. We show that by targeting GAB1 and smoothes the MEK / ERK signaling, mir-US5-2 indirectly regulating the expression EGR1 and UL138, which implicates critical miRNA regulation latency.IMPORTANCE HCMV Human cytomegalovirus (HCMV) causes significant illness in immunocompromised individuals, including transplant patients. HCMV establishes latency in the hematopoietic stem cells in the bone marrow.
The mechanisms that regulate the latency and reactivation of viral replication is complex and not fully understood. HCMV-encoded miRNAs are small regulatory RNA that reduces expression of the protein. In this study, we found that HCMV miRNA miR-US5-2 targeting the epidermal growth factor receptor (EGFR) protein GAB1 adapter that directly affect downstream cellular signaling pathways activated by EGF. As a result, mir-US5-2 block EGF-mediated proliferation of human fibroblasts. early growth response gene 1 (EGR1) is a transcription factor activated by EGFR signaling that regulates the expression of HCMV UL138.
We show that miR-UL138 US5-2 regulates expression via downregulation GAB1-mediated signaling pathways that lead to the expression of EGR1. These data demonstrate that miR-US5-2, through downregulation of GAB1, can play an important role during the reactivation from latency by reducing the proliferation and expression of UL138.
Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and UL138 Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways
MKP-1 overproduction associated with chemoresistance in bladder cancer through the MAPK pathway
Mitogen-activated protein kinase phosphatase-1 (MKP-1) has been revealed to be expressed in bladder cancer, especially in non-muscle invasive bladder cancer. MKP-1 may also be associated with chemotherapy resistance. However, the underlying mechanism has not been elucidated. The current study examined the expression of MKP-1 by immunohistochemistry on surgical resection specimens obtained from patients with primary and recurrent bladder cancer.
The results showed that MKP-1 expression is increased in patients with recurrent. In addition, the 3D model of the line of human bladder cancer cells, RT112, was established to determine the role of MKP-1 in drug resistance. The results show that MKP-1 overproduction protected cells against bladder cancer cell death. Instead, MKP-1 knockdown lowered to sensitize cells to die.
Description: A polyclonal antibody against FRS2. Recognizes FRS2 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/40000
Description: A polyclonal antibody against FRS2. Recognizes FRS2 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/5000
Description: A polyclonal antibody against FRS2. Recognizes FRS2 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC
Description: A polyclonal antibody against FRS2. Recognizes FRS2 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC; Recommended dilution: IHC:1:20-1:200
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y196
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y196
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y196
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y436
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y436
Description: A polyclonal antibody for detection of FRS2 from Human, Mouse. This FRS2 antibody is for WB, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human FRS2 around the non-phosphorylation site of Y436
Description: Adapter protein that links FGR and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.
Description: Adapter protein that links FGR and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.
Description: Adapter protein that links FGR and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.
Description: Fibroblast growth factor (FGF) receptor substrate 2 (FRS2) has an alternative name as SNT-1, it is an adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. FRS2 is a 508 amino-acid protein, which is phosphorylated on tyrosine residues. The molecular weight of non-phosphorylated FRS2 is 57-68 kDa, but phosphorylated FRS2 is 80-90 kDa. Phosphorylation of FRS2 is associated with activation of a number of MAP kinases. Allele-specific regulation of FGFR2 mRNA expression with a mildly increased breast cancer risk has been reported.
Description: Fibroblast growth factor (FGF) receptor substrate 2 (FRS2) has an alternative name as SNT-1, it is an adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. FRS2 is a 508 amino-acid protein, which is phosphorylated on tyrosine residues. The molecular weight of non-phosphorylated FRS2 is 57-68 kDa, but phosphorylated FRS2 is 80-90 kDa. Phosphorylation of FRS2 is associated with activation of a number of MAP kinases. Allele-specific regulation of FGFR2 mRNA expression with a mildly increased breast cancer risk has been reported.
Description: Fibroblast growth factor (FGF) receptor substrate 2 (FRS2) has an alternative name as SNT-1, it is an adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. FRS2 is a 508 amino-acid protein, which is phosphorylated on tyrosine residues. The molecular weight of non-phosphorylated FRS2 is 57-68 kDa, but phosphorylated FRS2 is 80-90 kDa. Phosphorylation of FRS2 is associated with activation of a number of MAP kinases. Allele-specific regulation of FGFR2 mRNA expression with a mildly increased breast cancer risk has been reported.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human FRS2 . This antibody is tested and proven to work in the following applications:
In addition, the application of MAPK inhibitors effectively increase the sensitivity of cells to pirarubicin RT112. In conclusion, the results of this study show that MKP-1 treatment resulted in bladder cancer cell chemoresistance through JNK, ERK and p38 pathways. MKP-1 can also serve as a potential therapeutic target for chemoresistance in patients with bladder cancer.
