Prolactin Induces SHP-2 Association with Stat5, Nuclear Translocation, and Binding to the β-Casein Gene Promoter in Mammary Cells

Chughtai, Naila; Schimchowitsch, Sarah; Lebrun, Jean-Jacques; Ali, Suhad

doi:10.1074/jbc.m200156200

Cited by 72 publications

(54 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous reports (Yu et al, 2000;Chughtai et al, 2002;Chen et al, 2003), anti-STAT5 immunoprecipitation followed by anti-SHP-2 immunoblotting showed that SHP-2 constitutively associated with STAT5 independent of IL-3 stimulation in SHP-2 overexpressing cells (data not shown). Further in vitro GST pull down assay demonstrated that only the phosphatase fragment could pull down STAT5 (data not shown), suggesting that the SHP-2/STAT5 interaction is direct and that this association is mediated by the C-terminal part of SHP-2 but not the SH2 domains.…”

Section: Shp-2 Phosphatase Associates With and Dephosphorylates Stat5supporting

confidence: 80%

“…STAT5 is phosphorylated and activated by Jak family kinases, particularly Jak2; however, it is not fully understood how this transcription factor is inactivated. Previous reports have suggested that STAT5 might be dephosphorylated by tyrosine phosphatases PTP1B and SHP-2 in the prolactin, IL-2, and erythropoietin signaling pathways (Aoki and Matsuda, 2000;Yu et al, 2000;Chughtai et al, 2002;Chen et al, 2003), but the biological significance of their functional interactions remains uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A negative role of SHP-2 tyrosine phosphatase in growth factor-dependent hematopoietic cell survival

Chen

Bunting

et al. 2004

Oncogene

View full text Add to dashboard Cite

SHP-2 tyrosine phosphatase is highly expressed in hematopoietic cells; however, the function of SHP-2 in hematopoietic cell processes is not fully understood. Recent identification of SHP-2 mutations in childhood leukemia further emphasizes the importance of SHP-2 regulation in hematopoietic cells. We previously reported that SHP-2 played a positive role in IL-3-induced activation of Jak2 kinase in a catalytic-dependent manner. Interestingly, enforced expression of wild-type (WT) SHP-2 in Ba/F3 cells enhanced growth factor deprivation-induced apoptosis. Biochemical analyses revealed that although IL-3 activation of Jak2 kinase was increased, tyrosyl phosphorylation of its downstream substrate STAT5 was disproportionately decreased by the overexpression of SHP-2. Following IL-3 deprivation, the tyrosyl phosphorylation of STAT5 that is required for its antiapoptotic activity was rapidly diminished in SHP-2 overexpressing cells. As a result, reduction of the putative downstream targets of STAT5-Bcl-X L and pim-1 was accelerated by overexpression of SHP-2. Further investigation showed that SHP-2 associated with STAT5, and that it was indeed able to dephosphorylate STAT5. Finally, overexpression of SHP-2 in primary bone marrow hematopoietic progenitor cells compromised their differentiative and proliferative potential, and enhanced growth factor withdrawal-induced cell death. And, the effect of SHP-2 overexpression on growth factor-dependent survival was diminished in STAT5-deficient hematopoietic cells. Taken together, these results suggest that SHP-2 tyrosine phosphatase negatively regulates hematopoietic cell survival by dephosphorylation of STAT5.

show abstract

Section: Shp-2 Phosphatase Associates With and Dephosphorylates Stat5supporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

A negative role of SHP-2 tyrosine phosphatase in growth factor-dependent hematopoietic cell survival

Chen

Bunting

et al. 2004

Oncogene

View full text Add to dashboard Cite

show abstract

“…Here, we used the T47D human breast cancer cell line, which is a model system for studies of PRL and EGF action in breast cancer biology (Das and Vonderhaar, 1996a, b;Haraguchi et al, 1997;Gibson et al, 1999;Maus et al, 1999;Badache and Hynes, 2001;Lichtner et al, 2001;Chen et al, 2002;Chughtai et al, 2002;Kassenbrock et al, 2002;Acosta et al, 2003). We first tested responsiveness to each stimulus in these cells.…”

Section: Prl Promotes Erk-dependent Threonine Phosphorylation Of Egfrmentioning

confidence: 99%

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Huang

Jiang

et al. 2006

Oncogene

View full text Add to dashboard Cite

Prolactin (PRL) is a polypeptide hormone produced by the anterior pituitary gland and other sites that acts both systemically and locally to cause lactation and other biological effects by interacting with the PRL receptor, a Janus kinase (JAK)2-coupled cytokine receptor family member, and activating downstream signal pathways. Recent evidence suggests PRL is a player in the pathogenesis and progression of breast cancer. Epidermal growth factor (EGF) also has effects on breast tissue, working through its receptors, epidermal growth factor receptor (EGFR) and ErbB-2 (c-neu, HER2), both intrinsic tyrosine kinase growth factor receptors. EGFR promotes pubertal breast ductal morphogenesis in mice, and both EGFR and ErbB-2 are relevant in pathogenesis and behavior of breast and other human cancers. Previous studies showed that PRL and EGF synergize to enhance motility in the human breast cancer cell line, T47D. In this study, we explored crosstalk between the PRL and EGF signaling pathways in T47D cells, with an ultimate aim of understanding how these two important factors might work together in vivo to affect breast cancer behavior. Both PRL and EGF caused robust signaling in T47D cells; PRL acutely activated JAK2, signal transducer and activator of transcription-5 (STAT5), and extracellular signal-regulated kinase-1 and -2 (ERK1 and ERK2), whereas EGF caused EGFR activation and consequent src homology collagen (SHC) activation and ERK activation. Notably, PRL also caused phosphorylation of the EGFR and ErbB-2 at sites detected by PTP101, an antibody that recognizes threonine phosphorylation at consensus motifs for ERK-induced phosphorylation. PRL-induced PTP101-reactive phosphorylation was prevented by pretreatment with PD98059, an ERK pathway inhibitor. Furthermore, PRL synergized with EGF in activating SHC and ERK and transactivating a luciferase reporter driven by c-fos gene enhancer elements, suggesting that PRL allowed markedly enhanced EGF signaling. This was accompanied by substantial inhibition of EGF-induced EGFR downregulation when PRL and EGF cotreatment was compared to EGF treatment alone. This effect of PRL was abrogated by ERK pathway inhibitor pretreatment. Our data suggest that PRL synergistically augments EGF signaling in T47D breast cancer cells at least in part by lessening EGF-induced EGFR downregulation and that this effect requires PRL-induced ERK activity and threonine phosphorylation of EGFR.

show abstract

“…The function of nuclear SHP-2 in prostate cancer could be involved in migration and invasion since nuclear expression correlated with extracapsular extension of the cancer. Prior studies have also reported SHP-2 in the nucleus [16][17][18][19]. Since SHP-2 lacks a typical nuclear localization signal sequence, it could be transported to the nucleus in association with proteins such as Gab1 [19].…”

Section: Correlation Of Shp-2 With Clinicopathological Parameters Andmentioning

confidence: 95%

“…Although it remains unclear, differential compartmentalization may alter SHP-2 function. For example, SHP-2 has been associated with the regulation of STAT5a as well as telomerase reverse transcriptase in the nucleus [17,19]. However, further studies are required to determine whether this PTP functions similarly in prostate cancer.…”

Section: Correlation Of Shp-2 With Clinicopathological Parameters Andmentioning

confidence: 99%

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes

et al. 2012

View full text Add to dashboard Cite

Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor specimens from 122 patients with prostate cancer were analyzed using a tissue microarray. Our data demonstrate that all four prostate cancer cell lines express the SHP-2 protein. Additionally, low staining intensity and SHP-2 expression in the cytoplasm of cancer cells in prostate tumor specimens was inversely correlated with prostate volume (p=0.041 and p=0.042, respectively) whereas nuclear staining was positively correlated with extracapsular extension (ece) (p=0.039). In our post-prostatectomy specimens, we found that patients with low SHP-2 expression had less-favorable outcomes with respect to biochemical recurrence (BCR) and clinical progression (p=0.005 and p=0.018 respectively). The loss of cytoplasmic SHP-2 expression is associated with increased growth and prostatic cancer progression.

show abstract

Prolactin Induces SHP-2 Association with Stat5, Nuclear Translocation, and Binding to the β-Casein Gene Promoter in Mammary Cells

Cited by 72 publications

References 37 publications

A negative role of SHP-2 tyrosine phosphatase in growth factor-dependent hematopoietic cell survival

A negative role of SHP-2 tyrosine phosphatase in growth factor-dependent hematopoietic cell survival

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes

Contact Info

Product

Resources

About