Regulation of Androgen Receptor Activity by Tyrosine Phosphorylation

Guo, Zhiyong; Dai, Bojie; Jiang, Tianyun; Xu, Kexin; Xie, Yingqiu; Kim, Oekyung; Nesheiwat, Issa; Kong, Xiangbin; Melamed, Jonathan; Handratta, Venkatesh; Njar, Vincent C.O.; Brodie, Angela; Yu, Li; Veenstra, Timothy D.; Chen, Hegang; Qiu, Yun

doi:10.1016/j.ccr.2006.12.010

Cited by 30 publications

(63 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the potential importance of p66 Shc in carcinogenesis, further studies are needed to clarify the correlation of p66 Shc expression with breast cancer. In summary, cross-talks between tyrosine phosphorylation signaling and steroid hormones have been well established (Weigel 1996, Meng et al 2000, Grossmann et al 2001, Guo et al 2006, Kraus et al 2006, Migliaccio et al 2006, Weigel & Moore 2007); it is thus reasonable to propose that p66 Shc mediates steroid action in steroid-responsive epithelial cells. We therefore hypothesize that the elevated level of p66 Shc protein in steroid-related cancer cells plays a critical role in up-regulating those cancer cell proliferation and thus contributes to the tumorigenicity of those cancers (Fig.…”

Section: Role Of Shc Proteins In Steroid-regulated Tumor Progression mentioning

confidence: 98%

“…These observations explain how the PTB domain localizes p52 Shc to the membrane where it becomes phosphorylated by cytoskeleton-associated tyrosine kinases, which finally results in cell migration. It should be noted that these non-receptor tyrosine kinases, e.g., Src, closely interact with steroid hormone signaling pathway (Migliaccio et al 2000, Guo et al 2006). The molecular mechanism by which steroids induce cell adhesion and/or migration via p52 Shc requires further investigation.…”

Section: Role Of Shc Proteins In Steroid-regulated Tumor Progression mentioning

confidence: 99%

See 1 more Smart Citation

A novel role of Shc adaptor proteins in steroid hormone-regulated cancers

Alam

Rajendran

Ouyang

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

Tyrosine phosphorylation plays a critical role in growth regulation, and its aberrant regulation can be involved in carcinogenesis. The association of Shc (Src homolog and collagen homolog) adaptor protein family members in tyrosine phosphorylation signaling pathway is well recognized. Shc adaptor proteins transmit activated tyrosine phosphorylation signaling that suggest their plausible role in growth regulation including carcinogenesis and metastasis. In parallel, by sharing a similar mechanism of carcinogenesis, the steroids are involved in the early stage of carcinogenesis as well as the regulation of cancer progression and metastatic processes. Recent evidence indicates a cross-talk between tyrosine phosphorylation signaling and steroid hormone action in epithelial cells, including prostate and breast cancer cells. Therefore, the members of Shc proteins may function as mediators between tyrosine phosphorylation and steroid signaling in steroid-regulated cell proliferation and carcinogenesis. In this communication, we discuss the novel roles of Shc proteins, specifically p52Shc and p66 Shc, in steroid hormone-regulated cancers and a novel molecular mechanism by which redox signaling induced by p66Shc mediates steroid action via a non-genomic pathway. The p66 Shc protein may serve as an effective biomarker for predicting cancer prognosis as well as a useful target for treatment.

show abstract

Section: Role Of Shc Proteins In Steroid-regulated Tumor Progression mentioning

confidence: 98%

Section: Role Of Shc Proteins In Steroid-regulated Tumor Progression mentioning

confidence: 99%

A novel role of Shc adaptor proteins in steroid hormone-regulated cancers

Alam

Rajendran

Ouyang

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Dasatinib is thought to mediate its inhibitory effect in PCa through inhibition of SFK kinase activity among other mechanisms [40,41]. Work by Guo et al demonstrated that ARs in hormone refractory prostate tumors have increased activity independent of androgen binding and directly linked it to phosphorylation by SFKs [42]. Thus inhibiting SFK activity via dasatinib offers an opportunity to directly target AR-independent pathways in PCa.…”

Section: Targeting Cell Signalingmentioning

confidence: 97%

Therapeutic Modulation of Prostate Cancer Metastasis

Krishna¹,

Bergan²

2014

Future Med. Chem.

View full text Add to dashboard Cite

Targeting prostate cancer metastasis has very high therapeutic potential. Prostate cancer is the second most common cause of cancer death among men in the USA, and death results from the development of metastatic disease. In order to metastasize, cancer cells must complete a series of steps that together constitute the metastatic cascade. Each step therefore offers the opportunity for therapeutic targeting. However, practical limitations have served as limiting roadblocks to successfully targeting the metastatic cascade. They include our still-emerging understanding of the underlying biology, as well as the fact that many of the dysregulated processes have critical functionality in otherwise normal cells. We provide a discussion of the underlying biology, as it relates to therapeutic targeting. Therapeutic inroads are rapidly being made, and we present a series of case studies to highlight key points. Finally, future perspectives related to drug discovery for antimetastatic agents are discussed.

show abstract

“…In ERα, phosphorylation of Tyr 537 in the hormone binding domain has been described, although others have not detected phosphorylation of this site, suggesting that the stoichiometry of phosphorylation may be low and/or it is only phosphorylated under specific conditions [Al-Dhaheri and Rowan, 2006; Arnold et al, 1995]. Two recent studies have shown that Src can phosphorylate AR on Tyr 534 in the amino-terminus of AR and there is some evidence that other tyrosines can be phosphorylated to a lesser extent [Guo et al, 2006; Kraus et al, 2006]. Consistent with the failure to detect tyrosine phosphorylation of AR previously, an analysis of AR in LNCaP cells revealed that tyrosine phosphorylation in response to hormone was a rapid and transient event.…”

Section: Receptor Phosphorylationmentioning

confidence: 99%

“…Consistent with the failure to detect tyrosine phosphorylation of AR previously, an analysis of AR in LNCaP cells revealed that tyrosine phosphorylation in response to hormone was a rapid and transient event. Using a phosphorylation site-specific antibody, Guo et al have shown that the site is phosphorylated in AR in prostate tumors [Guo et al, 2006]. …”

Section: Receptor Phosphorylationmentioning

confidence: 99%

Kinases and protein phosphorylation as regulators of steroid hormone action

Weigel

Moore

2007

Nucl Recept Signal

View full text Add to dashboard Cite

Although the primary signal for the activation of steroid hormone receptors is binding of hormone, there is increasing evidence that the activities of cell signaling pathways and the phosphorylation status of these transcription factors and their coregulators determine the overall response to the hormone. In some cases, enhanced cell signaling is sufficient to cause activation of receptors in medium depleted of steroids. Steroid receptors are targets for multiple kinases. Many of the phosphorylation sites contain Ser/Thr-Pro motifs implicating proline-directed kinases such as the cyclin-dependent kinases and the mitogen-activated kinases (MAPK) in receptor phosphorylation. Although some sites are constitutively phosphorylated, others are phosphorylated in response to hormone. Still others are only phosphorylated in response to specific cell signaling pathways. Phosphorylation of specific sites has been implicated not only in overall transcriptional activity, but also in nuclear localization, protein stability, and DNA binding. The studies of the roles of phosphorylation in coregulator function are more limited, but it is now well established that many of them are highly phosphorylated and that phosphorylation regulates their function. There is good evidence that some of the phosphorylation sites in the receptors and coregulators are targets of multiple signaling pathways. Individual sites have been associated both with functions that enhance the activity of the receptor, as well as with functions that inhibit activity. Thus, the specific combinations of phosphorylations of the steroid receptor combined with the expression levels and phosphorylation status of coregulators will determine the genes regulated and the biological response. p53-induced serine/threonine phosphatase, protein phosphatase 1D magnesium-dependent, delta isoforms; PR: progesterone receptor; PSA: prostate specific antigen; SMRT: silencing mediator of retinoid and thyroid hormone receptors; SPBP: stromelysin-1 platelet-derived growth factor-responsive element-binding protein; SRC-1: steroid receptor coactivator-1; TIF2: transcription intermediary factor 2; TRAP220: thyroid receptor associated protein 220 |

show abstract

Regulation of Androgen Receptor Activity by Tyrosine Phosphorylation

Cited by 30 publications

References 0 publications

A novel role of Shc adaptor proteins in steroid hormone-regulated cancers

A novel role of Shc adaptor proteins in steroid hormone-regulated cancers

Therapeutic Modulation of Prostate Cancer Metastasis

Kinases and protein phosphorylation as regulators of steroid hormone action

Contact Info

Product

Resources

About