PMID- 2553748
OWN - NLM
STAT- MEDLINE
DCOM- 19891205
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 109
IP  - 5
DP  - 1989 Nov
TI  - Signal transduction by epidermal growth factor occurs through the subclass of 
      high affinity receptors.
PG  - 2495-507
AB  - Many cell types display two classes of epidermal growth factor receptor (EGFR) as 
      judged from EGF binding studies; i.e., a major class of low affinity EGFR and a 
      minor class of high affinity EGFR. We have studied their respective contribution 
      to the cascade of events elicited by EGF in human A431 carcinoma cells, using 
      anti-EGFR mAb 2E9. This antibody specifically blocks EGF binding to low affinity 
      EGFR, without activating receptors in intact cells, and thus enables us to study 
      the effects of exclusive EGF binding to high affinity EGFR. We show that blocking 
      of low affinity EGFR by mAb 2E9 has almost no effect on the activation of the 
      receptor protein-tyrosine kinase by EGF, suggesting that EGFR kinase activation 
      occurs exclusively through the subclass of high affinity EGFR (5-10%). In 
      addition, we provide evidence that high affinity EGFR exists both in monomeric 
      and dimeric forms, and that cross-phosphorylation of low affinity EGFR by high 
      affinity EGFR may take place in dimers of both receptor types. We demonstrate 
      that the following early cellular response to EGF are also unimpaired in the 
      presence of mAb 2E9: (a) inositol phosphate production, (b) release of Ca2+ from 
      intracellular stores, (c) rise in intracellular pH, (d) phosphorylation of EGF on 
      threonine residue 654, (e) induction of c-fos gene expression, and (f) alteration 
      in cell morphology. As possible nonspecific side effects, we observed that the 
      EGF induced Ca2+ influx and fluid-phase pinocytosis were inhibited in A431 cells 
      in the presence of mAb 2E9. We conclude, therefore, that the activation of the 
      EGFR signal transduction cascade can occur completely through exclusive binding 
      of EGF to the subclass of high affinity EGFR.
FAU - Defize, L H
AU  - Defize LH
AD  - Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
FAU - Boonstra, J
AU  - Boonstra J
FAU - Meisenhelder, J
AU  - Meisenhelder J
FAU - Kruijer, W
AU  - Kruijer W
FAU - Tertoolen, L G
AU  - Tertoolen LG
FAU - Tilly, B C
AU  - Tilly BC
FAU - Hunter, T
AU  - Hunter T
FAU - van Bergen en Henegouwen, P M
AU  - van Bergen en Henegouwen PM
FAU - Moolenaar, W H
AU  - Moolenaar WH
FAU - de Laat, S W
AU  - de Laat SW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Cell Line
MH  - Epidermal Growth Factor/metabolism/*pharmacology/physiology
MH  - ErbB Receptors/metabolism/*physiology
MH  - Humans
MH  - Kinetics
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - *Signal Transduction
MH  - Tumor Cells, Cultured/cytology/drug effects/physiology
PMC - PMC2115872
EDAT- 1989/11/01 00:00
MHDA- 1989/11/01 00:01
PMCR- 1990/05/01
CRDT- 1989/11/01 00:00
PHST- 1989/11/01 00:00 [pubmed]
PHST- 1989/11/01 00:01 [medline]
PHST- 1989/11/01 00:00 [entrez]
PHST- 1990/05/01 00:00 [pmc-release]
AID - 90037242 [pii]
AID - 10.1083/jcb.109.5.2495 [doi]
PST - ppublish
SO  - J Cell Biol. 1989 Nov;109(5):2495-507. doi: 10.1083/jcb.109.5.2495.