PMID- 8530448 OWN - NLM STAT- MEDLINE DCOM- 19960130 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 270 IP - 51 DP - 1995 Dec 22 TI - Urokinase-type plasminogen activator-induced monocyte adhesion requires a carboxyl-terminal lysine and cAMP-dependent signal transduction. PG - 30282-5 AB - 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. FAU - Li, C AU - Li C AD - Vascular Research Laboratory, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. FAU - Liu, J N AU - Liu JN FAU - Gurewich, V AU - Gurewich V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (PLAUR protein, human) RN - 0 (Peptide Fragments) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Urokinase Plasminogen Activator) RN - 12UHW9R67N (Isoflurophate) RN - 1CC1JFE158 (Dactinomycin) RN - 1F7A44V6OU (Colforsin) RN - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate) RN - 31356-94-2 (8-bromocyclic GMP) RN - 98600C0908 (Cycloheximide) RN - E0399OZS9N (Cyclic AMP) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology MH - Binding Sites MH - Cell Adhesion/drug effects/*physiology MH - Cell Line MH - Colforsin/pharmacology MH - Cyclic AMP/*metabolism MH - Cyclic GMP/analogs & derivatives/pharmacology MH - Cycloheximide/pharmacology MH - Dactinomycin/pharmacology MH - Humans MH - Isoflurophate/pharmacology MH - Kinetics MH - Monocytes/drug effects/*physiology MH - Peptide Fragments/pharmacology MH - Receptors, Cell Surface/metabolism MH - Receptors, Urokinase Plasminogen Activator MH - Urokinase-Type Plasminogen Activator/*pharmacology EDAT- 1995/12/22 00:00 MHDA- 1995/12/22 00:01 CRDT- 1995/12/22 00:00 PHST- 1995/12/22 00:00 [pubmed] PHST- 1995/12/22 00:01 [medline] PHST- 1995/12/22 00:00 [entrez] AID - S0021-9258(17)31128-6 [pii] AID - 10.1074/jbc.270.51.30282 [doi] PST - ppublish SO - J Biol Chem. 1995 Dec 22;270(51):30282-5. doi: 10.1074/jbc.270.51.30282.