Phosphorylation of a surface receptor bound urokinase-type plasminogen activator in a human metastatic carcinomatous cell line

Takahashi, Kei; Kwaan, Hau C.; Ikeo, Kazuho; Koh, Enki

doi:10.1016/0006-291x(92)91899-2

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…In contrast, a specific receptor for tPA on the tumor cell surface has not yet been found; thus, tPA is not protected from inhibition by the PAls. Membrane-bound uPA is phosphorylated resulting in a 60% decrease in its reactivity with the PAls, while at the same time, altering its catalytic efficiency with a five-fold increase in its Kcat [111][112]. A similar picture has not yet been observed with tPA.…”

Section: Mechanism: Facilitating Cell Migrationmentioning

confidence: 68%

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The plasminogen-plasmin system in malignancy

1992

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The study of the plasminogen-plasmin system has, in the past, contributed much to the understanding of fibrinolysis and thrombolysis. Attention is now focused on the role of the components of this system in many biologic functions. Findings of uPA, its receptor and its inhibitor in many tumor tissues and tumor cell lines, strongly implicate their involvement in tumor invasion, tumor cell proliferation and metastasis. The characteristics of the plasminogen activators, the uPA receptor and the plasminogen activator inhibitors as well as their expression and regulation in tumors and tumor cell lines are reviewed.

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Section: Mechanism: Facilitating Cell Migrationmentioning

confidence: 68%

“…7. Further analysis revealed that phosphorylation of the uPA occurs during transportation to cell surface from the cytosol [111,112]. The six tyrosine residues in the ATF is phosphorylated by the src pp60 endogenous protein kinase and serine residues by protein kinase C respectively.…”

Section: Plasminogen Activator Inhibitors (Palsmentioning

confidence: 99%

The plasminogen-plasmin system in malignancy

1992

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“…Receptor-bound uPA is phosphorylated and stabilized compared with free uPA [19,20] and uPA is a membrane-bound active enzyme [21]. In our experiment not only free uPA but also recep tor-bound uPA may be stained with anti-uPA antibody.…”

Section: Discussionmentioning

confidence: 94%

Association of Immunohistochemical Detection of Urokinase-Type Plasminogen Activator with Metastasis and Prognosis in Colorectal Cancer

Sato

Nishimura²,

Yonemura³

et al. 1995

Oncology

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We evaluated urokinase-type plasminogen activator (uPA) expression with immunohistochemistry in 90 cases of colorectal cancer and compared it with the clinicopathological findings. Patients who had cancer cells which were stained intensively relative to the background were recognized as uPA-posi-tive patients. The uPA-positive rate was 36.7% (33/90) in total cases. There was a significant correlation between uPA expression and lymph node metastasis. A significant correlation was also seen between uPA expression and liver metastasis. Prognosis was poorer in the uPA-positive patients than in the uPA-negative patients. Therefore, uPA may be a good predictor of metastasis and prognosis.

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“…This shift in the pI of Pg 2ε may be associated with phosphorylation of the Pg molecule [63]. In this context, a shift in the pI of u-PA from 9.2 to 7.6, secondary to the phosphorylation of Tyr and Ser residues, is associated with the activation of pp60 src and of protein kinase C in metastatic tumour cells [64][65][66]. However, no data are available with respect to the kinases involved in the phosphorylation of Pg and u-PA, or its role in the multiple biological functions exerted by these proteins.…”

Section: Discussionmentioning

confidence: 99%

Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal transduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells

Gonzalez-Gronow¹,

Grenett²,

Weber³

et al. 2001

Biochem. J.

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Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are involved in the proteolytic degradation of extracellular matrix components, a requisite event for malignant cell metastasis. The highly invasive 1-LN human prostate tumour cell line synthesizes and secretes large amounts of Pg activators and MMPs. We demonstrate here that the Pg type 2 (Pg 2) receptor in these cells is composed primarily of the membrane glycoprotein dipeptidyl peptidase IV (DPP IV). Pg 2 has six glycoforms that differ in their sialic acid content. Only the highly sialylated Pg 2γ, Pg 2δ and Pg 2ε glycoforms bind to DPP IV via their carbohydrate chains and induce a Ca# + signalling cascade ; Abbreviations used : ECM, extracellular matrix ; MMP, matrix metalloproteinase ; Pg, plasminogen ; DPP IV, dipeptidyl peptidase IV (CD26) ; u-PA, urinary-type plasminogen activator ; t-PA, tissue-type plasminogen activator ; mAb, monoclonal antibody ; FAPα, fibroblast activation protein α ; HBSS, Hanks balanced salt solution ; fura 2/AM, fura 2 acetoxymethyl ester ; 6-AHA, 6-aminohexanoic acid ; [Ca 2 + ] i , cytosolic free Ca 2 + concentration ; GAPDH, glyceraldehyde-3-phosphate dehydrogenase. 1 To whom correspondence should be addressed (e-mail gonza002!mc.duke.edu). however, Pg 2ε alone is also able to significantly stimulate expression of MMP-9. We further demonstrate that the Pgmediated invasive activity of 1-LN cells is dependent on the availability of Pg 2ε. This is the first demonstration of a direct association between the expression of MMP-9 and the Pg activation system.

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Phosphorylation of a surface receptor bound urokinase-type plasminogen activator in a human metastatic carcinomatous cell line

Cited by 16 publications

References 29 publications

The plasminogen-plasmin system in malignancy

The plasminogen-plasmin system in malignancy

Association of Immunohistochemical Detection of Urokinase-Type Plasminogen Activator with Metastasis and Prognosis in Colorectal Cancer

Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal transduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells

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