Urokinase-type Plasminogen Activator-induced Monocyte Adhesion Requires a Carboxyl-terminal Lysine and cAMP-dependent Signal Transduction (∗)

• Published in: The Journal of biological chemistry Vol. 270; no. 51; pp. 30282 - 30285
• Main Authors: Li, Cuizhen, Liu, Jian-Ning, Gurewich, Victor
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-12-1995; American Society for Biochemistry and Molecular Biology
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Binding Sites; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Line; Colforsin - pharmacology; Cyclic AMP - metabolism; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Humans; Isoflurophate - pharmacology; Kinetics; Monocytes - drug effects; Monocytes - physiology; Peptide Fragments - pharmacology; Receptors, Cell Surface - metabolism; Receptors, Urokinase Plasminogen Activator; Urokinase-Type Plasminogen Activator - pharmacology; Vibrio cholerae
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.51.30282

Urokinase-type plasminogen activator (u-PA) or its amino-terminal fragment (ATF) containing the u-PA receptor (u-PAR) binding domain, is known to promote monocyte adhesion. In the present study, U937 monocyte adhesion to a plastic surface was used to investigate the mechanism of its promotion by u-PA and ATF. Adhesion was found to be inhibited by cycloheximide or actinomycin D, implicating protein synthesis and gene expression in u-PA-induced monocyte adhesion. Adhesion was prevented by 2′-deoxyadenosine 3′-monophosphate, indicating that a cAMP-dependent pathway of signal transduction was involved. This concept was supported by the complementary finding that u-PA-induced adhesion was greatly promoted by forskolin, cholera toxin, or 8-bromo-cAMP, which by themselves induced little adhesion. Furthermore, similar to many other cAMP-dependent activities, cGMP diminished u-PA-induced adhesion. When u-PA or ATF was treated with immobilized carboxypeptidase B, its proadhesive effect was abolished, implicating the involvement of carboxyl-terminal lysine residues (Lys158 on u-PA and Lys135 on ATF). Moreover, when a carboxyl-terminal lysine analog was added, the proadhesive effect of carboxypeptidase B-treated u-PA or ATF was restored. In conclusion, the present study indicates that u-PA- or ATF-induced monocyte adhesion involves cAMP-dependent signal transduction, which is triggered by u-PAR binding. It is also critically dependent on the presence of a carboxyl-terminal lysine.