PMID- 6327695
OWN - NLM
STAT- MEDLINE
DCOM- 19840716
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 259
IP  - 11
DP  - 1984 Jun 10
TI  - Ganglioside-mediated modulation of cell growth, growth factor binding, and 
      receptor phosphorylation.
PG  - 6818-25
AB  - Glycosphingolipids added exogenously in cell culture are slowly incorporated into 
      plasma membranes, inhibit cell growth, and modify growth behavior ( Laine , R. 
      A., and Hakomori, S. (1973) Biochem. Biophys. Res. Commun. 54, 1039-1045; Keenan 
      , T. W., Schmid, E., Franke , W. W., and Wiegandt , H. (1975) Exp. Cell Res. 92, 
      259-270). With the availability of purified growth factors and serum-free culture 
      conditions in recent years, we have been able to examine this phenomenon in mouse 
      Swiss 3T3 cells in greater detail with the following results. 1) Cell growth 
      (cell number increase) in serum-free medium was specifically inhibited by the 
      presence of GM1 and to a lesser extent by GM3, but not by NeuAcnLc4 , although 
      the gangliosides were incorporated equally well into cell membranes. GM3 
      inhibited both platelet-derived growth factor (PDGF)- and epidermal growth 
      factor-stimulated mitogenesis determined by thymidine incorporation, while GM1 
      could only inhibit PDGF-stimulated mitogenesis. NeuAcnLc4 had no effect on 
      mitogen-stimulated thymidine incorporation. 2) The concentration-dependent 
      binding of 125I-PDGF binding to cells indicated that cells whose growth was 
      inhibited by GM1 or GM3 showed an increased affinity for PDGF as compared to 
      cells grown without addition of ganglioside, while the total number of receptors 
      stayed the same. Addition of ganglioside did not affect the binding of 125I-EGF. 
      3) No direct interaction was observed between gangliosides and growth factors as 
      evidenced by the lack of competition by ganglioside-containing liposomes for 
      cellular binding of 125I growth factors. 4) GM1 and GM3, but neither NeuAcnLc4 
      nor Gb4 , inhibited the PDGF-stimulated tyrosine phosphorylation by membrane 
      preparations of a 170,000 molecular weight protein, which is probably the PDGF 
      receptor. Thus, the level of gangliosides GM1 and GM3 in membranes may modulate 
      PDGF receptor function by affecting the degree of tyrosine phosphorylation and 
      may alter the affinity of the receptor for PDGF.
FAU - Bremer, E G
AU  - Bremer EG
FAU - Hakomori, S
AU  - Hakomori S
FAU - Bowen-Pope, D F
AU  - Bowen-Pope DF
FAU - Raines, E
AU  - Raines E
FAU - Ross, R
AU  - Ross R
LA  - eng
GR  - CA20026/CA/NCI NIH HHS/United States
GR  - HL18645/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (G(M3) Ganglioside)
RN  - 0 (Gangliosides)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Receptors, Cell Surface)
RN  - 37758-47-7 (G(M1) Ganglioside)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Epidermal Growth Factor/*metabolism
MH  - ErbB Receptors
MH  - G(M1) Ganglioside/*pharmacology
MH  - G(M3) Ganglioside/*pharmacology
MH  - Gangliosides/*pharmacology
MH  - Mice
MH  - Molecular Weight
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/*metabolism
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Platelet-Derived Growth Factor
MH  - Thymidine/metabolism
EDAT- 1984/06/10 00:00
MHDA- 1984/06/10 00:01
CRDT- 1984/06/10 00:00
PHST- 1984/06/10 00:00 [pubmed]
PHST- 1984/06/10 00:01 [medline]
PHST- 1984/06/10 00:00 [entrez]
AID - S0021-9258(17)39801-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1984 Jun 10;259(11):6818-25.