Cleavage of urokinase receptor regulates its interaction with integrins in thyroid cells.
The urokinase-type plasminogen activator uPA-R can regulate integrin functions by associating with several types of beta-subunit. We have recently shown that normal thyroid TAD-2 cells express both a native and a cleaved form of uPA-R which lacks the binding domain for uPA. We found this cleaved form to be present in reduced amounts in papillary and follicular thyroid carcinoma cells and completely absent in cells derived from an anaplastic thyroid carcinoma (ARO). We now report that in normal thyroid cells the intact form of uPA-R strongly associates with beta-1 integrins, whereas its cleaved form does not. uPA-R expressed by ARO cells shows a stronger resistance to the cleavage mediated by uPA, plasmin and chymotrypsin than does uPA-R expressed by normal thyroid cells. This resistance to cleavage correlates with the higher level of glycosylation of uPA-R of ARO cells as compared to that of cleavable uPA-R of normal thyroid cells. These results suggest that uPA-R cleavage, which occurs in several cell types, represents a mechanism regulating the interactions of uPA-R with integrins and, possibly, the subsequent integrin-mediated cell adhesion. Moreover we hypothesize that glycosylation regulates uPA-R cleavage and, indirectly, its interaction with integrins.
Montuori
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Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli, Naples, Italy.
Rossi
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Ragno
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D000581:Amidohydrolases / Q000378:metabolism; D002460:Cell Line; D002918:Chymotrypsin / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D010957:Plasmids; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D013961:Thyroid Gland; D014162:Transfection
D016023:Integrins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D002918:Chymotrypsin; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase