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Pollak, Michael; Beamer, Wes; Zhang, Jianchun

doi:10.1023/a:1006154108619

Cited by 141 publications

(23 citation statements)

References 53 publications

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“…This will lead to an increase of bioavailable IGFs, allowing them to bind and activate type 1 IGF receptor (48,51,67) and indirectly modulate cell survival, mitogenesis, and differentiation. By this way, hK5 might play a role in tumorigenesis (67,68) and particularly in prostate cancer progression (69).…”

Section: Discussionmentioning

confidence: 99%

Human Tissue Kallikrein 5 Is a Member of a Proteolytic Cascade Pathway Involved in Seminal Clot Liquefaction and Potentially in Prostate Cancer Progression

Michael

Pampalakis

Mikolajczyk

et al. 2006

Journal of Biological Chemistry

100

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Human tissue kallikreins (hKs) are a family of fifteen serine proteases. Several lines of evidence suggest that hKs participate in proteolytic cascade pathways. Human kallikrein 5 (hK5) has trypsinlike activity, is able to self-activate, and is co-expressed in various tissues with other hKs. In this study, we examined the ability of hK5 to activate other hKs. By using synthetic heptapeptides that encompass the activation site of each kallikrein and recombinant pro-hKs, we demonstrated that hK5 is able to activate pro-hK2 and pro-hK3. We then showed that, following their activation, hK5 can internally cleave and deactivate hK2 and hK3. Given the predominant expression of hK2 and hK3 in the prostate, we examined the pathophysiological role of hK5 in this tissue. We studied the regulation of hK5 activity by cations (Zn 2؉ , Ca 2؉ , Mg 2؉ , Na ؉ , and K ؉ ) and citrate and showed that Zn 2؉ can efficiently inhibit hK5 activity at levels well below its normal concentration in the prostate. We also show that hK5 can degrade semenogelins I and II, the major components of the seminal clot. Semenogelins can reverse the inhibition of hK5 by Zn 2؉ , providing a novel regulatory mechanism of its serine protease activity. hK5 is also able to internally cleave insulin-like growth factor-binding proteins 1, 2, 3, 4, and 5, but not 6, suggesting that it might be involved in prostate cancer progression through growth factor regulation. Our results uncover a kallikrein proteolytic cascade pathway in the prostate that participates in seminal clot liquefaction and probably in prostate cancer progression.

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Section: Discussionmentioning

confidence: 99%

Human Tissue Kallikrein 5 Is a Member of a Proteolytic Cascade Pathway Involved in Seminal Clot Liquefaction and Potentially in Prostate Cancer Progression

Michael

Pampalakis

Mikolajczyk

et al. 2006

Journal of Biological Chemistry

100

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“…Several reports have suggested that PSA may act as a tumor suppressor, a negative regulator of cell growth, and an apoptotic molecule [33,34,35], whereas, others suggest that PSA may, through its serine protease activity, promote tumor progression and metastasis [36,37,38]. The precise relationship between the reported functions of PSA in prostate cancer cells in vitro and the biological role of PSA as a serine protease in human prostate cancer in vivo is unknown.…”

Section: Discussionmentioning

confidence: 99%

Thiophilic-interaction chromatography of enzymatically active tissue prostate-specific antigen (T-PSA) and its modulation by zinc ions

Babu

Vijayalakshmi

Smith

et al. 2008

Journal of Chromatography B

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Prostate-specific antigen (PSA) is a serine protease secreted both by normal prostate glandular epithelia cells and prostate cancer cells. We explored "thiophilic-interaction chromatography" (TIC) to isolate tissue prostate-specific antigen (T-PSA) from fresh human prostate cancer tissue harvested by radical prostatectomy for the purpose to characterize T-PSA for its enzymatic activity and sensitivity to zinc ions. We have shown, for the first time, that T-PSA has strong affinity for the thiophilic gel (T-gel). The average recovery of T-PSA from T-gel is over 87%. The presence of PSA in the column eluate was confirmed by ELISA and SDS/PAGE. Western blot developed with monoclonal antibody to PSA revealed that T-PSA was predominantly in the "free" form having a molecular weight of 33kDA. Furthermore, T-PSA was found to be enzymatically active. T-PSA was found to be less enzymatically active as compared to seminal plasma PSA. The inhibition of enzymatic activity of both f-PSA and T PSA over a wide range of concentrations of Zn 2+ ions (10 nM to 50 μM) was comparable. In contrast, the enzymatic activity of chymotrypsin, another serineprotease, was affected differently. At higher concentrations of Zn 2+ (10 μM and higher) the enzymatic activity of chymotrypsin was inhibited, whereas, at lower concentrations of Zn 2+ (5 μM and lower), the enzymatic activity was enhanced.

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“…Among the various suggested mechanisms by which AR may be reactivated in a low androgen environment (7), signaling by growth factors, especially insulin-like growth factor 1 (IGF1), is reportedly of significant importance (8 -11). High IGF1 serum levels are correlated with an increased risk of PC (8,9), whereas IGF1 enhances AR transactivation under very low or absent androgen levels (12,13) and promotes PC cell proliferation (10). Recent studies have also revealed that high serum insulin levels are associated with an increased incidence of PC (14,15), although there is a lack of mechanistic studies implicating insulin signaling in the regulation of AR function.…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

Insulin-like Growth Factor 1/Insulin Signaling Activates Androgen Signaling through Direct Interactions of Foxo1 with Androgen Receptor

Fan

Yanase

Morinaga

et al. 2007

Journal of Biological Chemistry

164

137

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Untitled

Cited by 141 publications

References 53 publications

Human Tissue Kallikrein 5 Is a Member of a Proteolytic Cascade Pathway Involved in Seminal Clot Liquefaction and Potentially in Prostate Cancer Progression

Human Tissue Kallikrein 5 Is a Member of a Proteolytic Cascade Pathway Involved in Seminal Clot Liquefaction and Potentially in Prostate Cancer Progression

Thiophilic-interaction chromatography of enzymatically active tissue prostate-specific antigen (T-PSA) and its modulation by zinc ions

Insulin-like Growth Factor 1/Insulin Signaling Activates Androgen Signaling through Direct Interactions of Foxo1 with Androgen Receptor

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