PMID- 10339491
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 11
DP  - 1999 Jun 1
TI  - Characterization of cell-associated plasminogen activation catalyzed by 
      urokinase-type plasminogen activator, but independent of urokinase receptor 
      (uPAR, CD87).
PG  - 3839-46
AB  - The 55-kD urokinase (uPA) receptor (uPAR, CD87) is capable of binding uPA and may 
      be involved in regulating cell-associated plasminogen activation and pericellular 
      proteolysis. While investigating the relationship between uPAR levels and plasmin 
      generation, we found that uPA-catalyzed plasminogen activation is stimulated by 
      cells which do not express uPAR. This uPAR-independent mechanism appears to be at 
      least as effective in vitro as uPAR-dependent stimulation, such that stimulation 
      on the order of 30-fold was observed, resulting from improvements in both 
      apparent kcat and apparent Km. The mechanism depends on simultaneous binding of 
      both uPA and plasminogen to the cell and requires the presence of the 
      amino-terminal fragment (ATF), available in single chain and two chain 
      high-molecular-weight uPA, but not low-molecular-weight uPA. Stimulation was 
      observed in all leukemic cell lines investigated at similar optimum 
      concentrations of 10(6) to 10(7) cells/mL and may be more general. A mechanism is 
      proposed whereby uPA can associate with binding sites on the cell surface of 
      lower affinity, but higher capacity than uPAR, but these are sufficient to 
      stimulate plasmin generation even at subphysiologic uPA concentrations. This 
      mechanism is likely to operate under conditions commonly used for in vitro 
      studies and may have some significance in vivo.
FAU - Longstaff, C
AU  - Longstaff C
AD  - The National Institute for Biological Standards and Control, South Mimms, 
      Hertfordshire, UK. clongstaff@nibsc.ac.uk
FAU - Merton, R E
AU  - Merton RE
FAU - Fabregas, P
AU  - Fabregas P
FAU - Felez, J
AU  - Felez J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (PLAUR protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Humans
MH  - Plasminogen/*metabolism
MH  - Plasminogen Activators/*metabolism/pharmacology
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/*metabolism/pharmacology
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - S0006-4971(20)59515-3 [pii]
PST - ppublish
SO  - Blood. 1999 Jun 1;93(11):3839-46.