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Production of second messengers following chemotactic and mitogenic urokinase-receptor interaction in human fibroblasts and mouse fibroblasts transfected with human urokinase receptor.
Exp Cell Res. 1994 Aug; 213(2):438-48.EC

Abstract

We studied urokinase-type plasminogen activator (u-PA)-dependent chemotaxis and DNA synthesis in both human fibroblasts and LB6 mouse fibroblasts transfected with human u-PA receptor (u-PAR) gene (LB6 clone 19). Both cell lines have receptors for the amino-terminal fragment of u-PA (u-PA-ATF). We observed that u-PA and u-PA-ATF stimulated chemotactic migration of both LB6 clone 19 cells and human fibroblasts, which could be impaired by down-regulation of protein kinase C (PKC) with phorbol myristate acetate (PMA). While LB6 clone 19 cells were unable to undergo mitosis following exposure to either u-PA or u-PA-ATF, human fibroblasts were stimulated to mitosis by exogenous addition of native u-PA, and u-PA-ATF was ineffective. The mitogenic activity of u-PA on human fibroblasts could also be impaired by down-regulation of PKC with PMA. We studied second messenger formation following u-PAR stimulation. Neither inositol lipid metabolism nor intracellular Ca2+ content were affected, while an increase of diacylglycerol (DAG) generation was observed. Such DAG formation was related to de novo synthesis from glucose and was dependent on ligand-receptor interaction. Both u-PA-ATF and the native u-PA molecule were able to stimulate DAG formation, u-PA being from three to fourfold more efficient than ATF. These data suggest that u-PAR stimulation per se is sufficient to trigger DAG formation. The native molecule confers on the cell an additional stimulus, possibly related with the activation of a u-PA-catalytic site-dependent substrate. Such stimulation allows the cell to reach the DAG threshold level required to trigger DNA synthesis.

Authors+Show Affiliations

Institute of General Pathology, Florence University, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8050501

Citation

Anichini, E, et al. "Production of Second Messengers Following Chemotactic and Mitogenic Urokinase-receptor Interaction in Human Fibroblasts and Mouse Fibroblasts Transfected With Human Urokinase Receptor." Experimental Cell Research, vol. 213, no. 2, 1994, pp. 438-48.
Anichini E, Fibbi G, Pucci M, et al. Production of second messengers following chemotactic and mitogenic urokinase-receptor interaction in human fibroblasts and mouse fibroblasts transfected with human urokinase receptor. Exp Cell Res. 1994;213(2):438-48.
Anichini, E., Fibbi, G., Pucci, M., Caldini, R., Chevanne, M., & Del Rosso, M. (1994). Production of second messengers following chemotactic and mitogenic urokinase-receptor interaction in human fibroblasts and mouse fibroblasts transfected with human urokinase receptor. Experimental Cell Research, 213(2), 438-48.
Anichini E, et al. Production of Second Messengers Following Chemotactic and Mitogenic Urokinase-receptor Interaction in Human Fibroblasts and Mouse Fibroblasts Transfected With Human Urokinase Receptor. Exp Cell Res. 1994;213(2):438-48. PubMed PMID: 8050501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Production of second messengers following chemotactic and mitogenic urokinase-receptor interaction in human fibroblasts and mouse fibroblasts transfected with human urokinase receptor. AU - Anichini,E, AU - Fibbi,G, AU - Pucci,M, AU - Caldini,R, AU - Chevanne,M, AU - Del Rosso,M, PY - 1994/8/1/pubmed PY - 1994/8/1/medline PY - 1994/8/1/entrez SP - 438 EP - 48 JF - Experimental cell research JO - Exp Cell Res VL - 213 IS - 2 N2 - We studied urokinase-type plasminogen activator (u-PA)-dependent chemotaxis and DNA synthesis in both human fibroblasts and LB6 mouse fibroblasts transfected with human u-PA receptor (u-PAR) gene (LB6 clone 19). Both cell lines have receptors for the amino-terminal fragment of u-PA (u-PA-ATF). We observed that u-PA and u-PA-ATF stimulated chemotactic migration of both LB6 clone 19 cells and human fibroblasts, which could be impaired by down-regulation of protein kinase C (PKC) with phorbol myristate acetate (PMA). While LB6 clone 19 cells were unable to undergo mitosis following exposure to either u-PA or u-PA-ATF, human fibroblasts were stimulated to mitosis by exogenous addition of native u-PA, and u-PA-ATF was ineffective. The mitogenic activity of u-PA on human fibroblasts could also be impaired by down-regulation of PKC with PMA. We studied second messenger formation following u-PAR stimulation. Neither inositol lipid metabolism nor intracellular Ca2+ content were affected, while an increase of diacylglycerol (DAG) generation was observed. Such DAG formation was related to de novo synthesis from glucose and was dependent on ligand-receptor interaction. Both u-PA-ATF and the native u-PA molecule were able to stimulate DAG formation, u-PA being from three to fourfold more efficient than ATF. These data suggest that u-PAR stimulation per se is sufficient to trigger DAG formation. The native molecule confers on the cell an additional stimulus, possibly related with the activation of a u-PA-catalytic site-dependent substrate. Such stimulation allows the cell to reach the DAG threshold level required to trigger DNA synthesis. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/8050501/Production_of_second_messengers_following_chemotactic_and_mitogenic_urokinase_receptor_interaction_in_human_fibroblasts_and_mouse_fibroblasts_transfected_with_human_urokinase_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(84)71221-3 DB - PRIME DP - Unbound Medicine ER -