Significance of Increased Phosphatase Activity of Bone at the Site of Osteoplastic Metastases Secondary to Carcinoma of the Prostate Gland

Gutman, Ethel Benedict; Sproul, Edith E.; Gutman, Alexander B.

doi:10.1158/ajc.1936.485a

Cited by 304 publications

(24 citation statements)

References 8 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since Gutman et al [25] reported a correlation between acid phosphatase levels in the serum and prostatic cancer, prostatic acid phosphatase has been used as a marker for prostatic adenocarcinoma [26 - …”

Section: Discussionmentioning

confidence: 99%

A phosphotyrosyl‐protein phosphatase activity associated with acid phosphatase from human prostate gland

Chernoff

Chen

et al. 1984

European Journal of Biochemistry

108

View full text Add to dashboard Cite

Using [32P]P-Tyr-IgG and [32P]P-Tyr-casein phosphorylated by pp6O"-"c as substrates, studies on the phosphotyrosyl-protein phosphatase activity in human prostate gland indicate that it is associated with prostatic acid phosphatase. Evidence to support this conclusion include the following : (a) these two enzymatic activities co-purify to apparent homogeneity; (b) they co-migrated on polyacrylamide gel electrophoresis, ion-exchange and gel filtration chromatographies; (c) the exhibit identical thermostability; and (d) the phosphotyrosyl-protein phosphatase activity is sensitive to inhibition by p-nitrophenyl phosphate and by several classical inhibitors of prostatic acid phosphatase including I.(+)-tartrate, molybdate, vanadate and NaF. The purified enzyme exhibits high specificity towards phosphotyrosyl-proteins with little activity towards several phosphoseryl-proteins and phosphothreonyl-proteins examined. The present findings indicate that prostatic acid phosphatase may function in vivo as a phosphotyrosyl-protein phosphatase.Several transforming proteins, such as-pp60" coded by onc genes of viral or cellular origin have been shown to possess phosphotyrosyl-protein (P-Tyr-protein) kinase activity [ 1 -91. P-Tyr-protein kinase activity has also been shown to be associated with receptors for growth-promoting peptides, such as epidermal growth factor (EGF) [lo, 1 I], platelet-derived growth factor (PDGF) [12, 131 and insulin [14, 151. These findings have led to the hypothesis that phosphorylation at Tyr residues in proteins plays an important role in cellular transformation and in regulation of cellular growth [16,17].Several studies concerning P-Tyr-protein phosphatase activity in animal tissues have appeared recently. Alkaline phosphatases of animal and bacterial origin [18,19] and an acid phosphatase activity in the plasma membrane of human astrocytoma [20] have been reported to exhibit high specificity towards P-Tyr-histones. On the other hand, various P-Tyrprotein phosphatases lacking activity towards low-molecularweight non-protein phosphoesters, such asp-nitrophenyl phosphate (pNpP), have also been described [21-241. In this communication we examine P-Tyr-protein phosphatase activity in human prostate gland. The results indicate that the major active species of P-Tyr-protein phosphatase activity in this tissue is associated with acid phosphatasese, which has served as a useful biological marker of metastatic prostatic carcinoma for the last four decades [25 -281.

show abstract

Section: Discussionmentioning

confidence: 99%

A phosphotyrosyl‐protein phosphatase activity associated with acid phosphatase from human prostate gland

Chernoff

Chen

et al. 1984

European Journal of Biochemistry

108

View full text Add to dashboard Cite

show abstract

“…: 803-777-2140; Fax: 803-777-9521; E-mail: lebioda@psc.sc.edu. 1 The abbreviations used are: PAP, prostatic acid phosphatase; NPT, Npropyl-L-tartramate; PEG, polyethylene glycol; SPM, S. cerevisiae (yeast) phosphoglycerate mutase; RFB, rat liver fructose-2,6-bisphosphatase.…”

Section: The Atomic Coordinates and Structure Factors (Access Code 2hmentioning

confidence: 99%

“…Human prostatic acid phosphatase (PAP) 1 has been of significant medical interest ever since tests screening for serum PAP levels were successfully used to diagnose and stage prostate cancer (1). Recently, the primary diagnostic protocol for detecting prostate cancer has shifted from evaluating serum PAP levels to utilizing the prostate specific antigen test.…”

mentioning

confidence: 99%

Structural Origins of l(+)-Tartrate Inhibition of Human Prostatic Acid Phosphatase

LaCount

Handy

Lebioda

1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 Å resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. Human prostatic acid phosphatase (PAP) 1 has been of significant medical interest ever since tests screening for serum PAP levels were successfully used to diagnose and stage prostate cancer (1). Recently, the primary diagnostic protocol for detecting prostate cancer has shifted from evaluating serum PAP levels to utilizing the prostate specific antigen test. However, accurately detecting serum PAP levels is still of considerable interest because of its effectiveness in staging metastatic prostatic cancer and evaluating the progress of chemotherapy in prostate cancer patients (2).PAP, which is produced by the prostate gland, is found in the seminal fluid at concentrations near 1 mg/ml (3). The enzyme is categorized as an acid phosphatase, because its optimum pH range is between 4 and 7. PAP belongs to the family of high molecular weight phosphatases. Mature PAP is active as a glycosylated homodimer with M r ϭ ϳ100,000. The enzyme is capable of hydrolyzing a wide spectrum of substrates including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins (4). The natural substrate for PAP is uncertain, thus, the discovery of the specific biological function is of great interest and awaits further investigations.The catalytic mechanism has been intensely studied and it was concluded that the enzyme should be classified as a histidine phosphatase (5). The crucial intermediate is phosphoroamidate, namely phosphohistidine. The rate-limiting step is the breakdown of this covalent phosphoenzyme intermediate through addition of a nucleophilic water molecule to phosphoroamidate with concomitant elimination of inorganic phosphate, via a S N 2 mechanism, to form a noncovalent binary enzyme-inorganic phosphate complex. Extensive studies of chemically modified enzyme and a series of site-directed mutants allowed Van Etten and co-workers (5) to propose a sound description of the catalytic process.L(ϩ)-Tartrate is a fairly good inhibitor of PAP (K i ϭ 2.9 ϫ 10 Ϫ5 M at pH 5.0). It is specific for acid phosphatases; in addition to PAP, it also inhibits homologous lysosomal acid phosphatases and acid phosphatases isolated from such tissues as liver, bone, and kidney, which are usually not present in the blood serum (6). The inhibition is...

show abstract

“…zer ACA 1 ) measures quantitatively the acid phosphatase Since the findings of Gutman et al (1) and Huggms & pf prostatic origin> and that the substrate used (sodium Hodges (2) that serum acid phosphatase (EC 3. 1.…”

Section: Introductionmentioning

confidence: 99%

The Determination of Acid Phosphatase of Prostatic Origin with the Automatic Clinical Analyzer (ACA, DuPont)

Rijn¹,

Boer²,

Klosse³

1980

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Summary: A critical evaluation of the determination of acid phosphatase of prostatic origin with the Du Pont ACA is reported. The affinity of the enzyme towards certain substrates, and the specificity of sodium thymolphthalein monophosphate as a substrate for prostatic acid phosphatase were investigated. The validity of this method, which is supposed to be specific for prostatic phosphatase is, however, limited; clinical data showed that related human acid phosphatases interfere and decrease the specificity of the determination.

show abstract

Significance of Increased Phosphatase Activity of Bone at the Site of Osteoplastic Metastases Secondary to Carcinoma of the Prostate Gland

Cited by 304 publications

References 8 publications

A phosphotyrosyl‐protein phosphatase activity associated with acid phosphatase from human prostate gland

A phosphotyrosyl‐protein phosphatase activity associated with acid phosphatase from human prostate gland

Structural Origins of l(+)-Tartrate Inhibition of Human Prostatic Acid Phosphatase

The Determination of Acid Phosphatase of Prostatic Origin with the Automatic Clinical Analyzer (ACA, DuPont)

Contact Info

Product

Resources

About