PMID- 7688216
OWN - NLM
STAT- MEDLINE
DCOM- 19930901
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 293 ( Pt 2)
IP  - Pt 2
DP  - 1993 Jul 15
TI  - Binding of platelet-derived growth factor-BB and transforming growth factor-beta 
      1 to alpha 2-macroglobulin in vitro and in vivo: comparison of 
      receptor-recognized and non-recognized alpha 2-macroglobulin conformations.
PG  - 443-50
AB  - alpha 2-Macroglobulin (alpha 2M) undergoes a major conformational change when 
      reacting with proteinases or primary amines. This conformational change has been 
      referred to as the 'slow' to 'fast' transformation based on the increase in alpha 
      2M mobility shown by non-denaturing PAGE. Previous studies demonstrated that many 
      cytokines, including transforming growth factor beta 1 (TGF-beta 1) and 
      interleukin-1 beta, bind preferentially or exclusively to alpha 2M which has 
      undergone conformational change. In this study, we demonstrate that 
      platelet-derived growth factor-BB (PDGF-BB) also binds preferentially to 
      conformationally transformed alpha 2M (alpha 2M-methylamine, alpha 2M-trypsin) in 
      vitro. Purified 125I-PDGF-BB-alpha 2M-methylamine complex cleared rapidly from 
      the circulation of mice via the alpha 2M 
      receptor/low-density-lipoprotein-receptor-related protein (alpha 2M-R/LRP). In 
      order to determine whether PDGF-BB or TGF-beta 1 binds to native alpha 2M, we 
      defined the native conformation by lack of interaction with alpha 2M-R/LRP 
      instead of electrophoretic mobility. 125I-PDGF-BB was incubated with 4.3 microM 
      native alpha 2M and 0.47 microM alpha 2M-methylamine. The 125I-PDGF-BB 
      distributed evenly between slow-form and fast-form alpha 2M without shifting the 
      electrophoretic mobility of either species. When the mixed preparation was 
      injected intravenously in mice, 125I-PDGF-BB-fast-form-alpha 2M cleared rapidly 
      and selectively from the circulation; 125I-PDGF-BB which was bound to slow-form 
      alpha 2M was stable in the blood (apparently not recognized by alpha 2M-R/LRP). 
      Therefore, while conformationally transformed alpha 2M binds PDGF-BB 
      preferentially in vitro, non-alpha 2M-R/LRP-recognized alpha 2M binds PDGF-BB as 
      well. Binding of 125I-PDGF-BB and 125I-TGF-beta 1 to alpha 2M was demonstrated in 
      vivo by injecting the free growth factors intravenously into mice. Plasma samples 
      which were subjected to non-denaturing PAGE and autoradiography demonstrated 
      binding of both growth factors exclusively to the slow-form of alpha 2M. 
      Therefore, under normal physiological conditions, native alpha 2M (non-alpha 
      2M-R/LRP-recognized) is the primary form of the proteinase inhibitor functioning 
      as a carrier of PDGF-BB and TGF-beta 1 in the blood.
FAU - Crookston, K P
AU  - Crookston KP
AD  - Department of Biochemistry, University of Virginia Health Sciences Center, 
      Charlottesville 22908.
FAU - Webb, D J
AU  - Webb DJ
FAU - Lamarre, J
AU  - Lamarre J
FAU - Gonias, S L
AU  - Gonias SL
LA  - eng
GR  - CA-53462/CA/NCI NIH HHS/United States
GR  - GM 07267/GM/NIGMS NIH HHS/United States
GR  - HL-02272/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Methylamines)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (alpha-Macroglobulins)
RN  - BSF23SJ79E (methylamine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cross-Linking Reagents
MH  - Humans
MH  - Iodine Radioisotopes
MH  - Low Density Lipoprotein Receptor-Related Protein-1
MH  - Methylamines/chemistry/metabolism
MH  - Mice
MH  - Platelet-Derived Growth Factor/chemistry/*metabolism
MH  - Protein Conformation
MH  - Radioligand Assay
MH  - Receptors, Immunologic/*metabolism
MH  - Transforming Growth Factor beta/blood/*metabolism
MH  - alpha-Macroglobulins/chemistry/*metabolism
PMC - PMC1134380
EDAT- 1993/07/15 00:00
MHDA- 1993/07/15 00:01
PMCR- 1993/07/15
CRDT- 1993/07/15 00:00
PHST- 1993/07/15 00:00 [pubmed]
PHST- 1993/07/15 00:01 [medline]
PHST- 1993/07/15 00:00 [entrez]
PHST- 1993/07/15 00:00 [pmc-release]
AID - 10.1042/bj2930443 [doi]
PST - ppublish
SO  - Biochem J. 1993 Jul 15;293 ( Pt 2)(Pt 2):443-50. doi: 10.1042/bj2930443.