PMID- 10198537
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20190831
IS  - 0140-0118 (Print)
IS  - 0140-0118 (Linking)
VI  - 36
IP  - 4
DP  - 1998 Jul
TI  - Comparative mitogenic potencies of EGF and TGF alpha and their dependence on 
      receptor-limitation versus ligand-limitation.
PG  - 499-507
AB  - Transforming growth factor alpha (TGF alpha) has been reported to be a more 
      potent agonist when compared to epidermal growth factor (EGF) in several systems 
      while acting via their common receptor, the epidermal growth factor receptor 
      (EGFR). It has been postulated that this increased potency is mediated by the 
      increased recycling of EGFR upon activation by TGF alpha as against receptor 
      activation by EGF. The authors test this hypothesis by simultaneously measuring 
      mitogenesis and the dynamics of surface receptor number in response to these 
      ligands in NR6 mouse fibroblasts expressing the EGFR. The data demonstrates that 
      increased receptor recycling due to endosomal dissociation of TGF alpha can 
      indeed realise an increased mitogenic potency relative to EGF under appropriate 
      cellular and experimental conditions (i.e. situations in which the increase in 
      the number of occupied receptors due to receptor sparing by TGF alpha represents 
      additional mitogenic signalling capacity). However, this difference in receptor 
      trafficking does not uniquely determine the relative potencies of these ligands 
      since TGF alpha is a less potent mitogen compared to EGF when experimental 
      conditions are dominated by the effects of ligand trafficking on growth factor 
      availability. Thus, the relative potencies of these growth factors are determined 
      in a given context by the relative importance of ligand and receptor trafficking 
      effects which determine the availability of these signalling components. These 
      results are consistent with a suggested model of hormone responsiveness which 
      favours dissociative ligands (such as TGF alpha) in receptor-limited situations 
      and non-dissociative ligands (such as EGF) in the case of ligand limitation.
FAU - Reddy, C C
AU  - Reddy CC
AD  - Department of Chemical Engineering, University of Illinois at Urbana-Champaign 
      61801, USA.
FAU - Wells, A
AU  - Wells A
FAU - Lauffenburger, D A
AU  - Lauffenburger DA
LA  - eng
GR  - CA69213/CA/NCI 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  - United States
TA  - Med Biol Eng Comput
JT  - Medical & biological engineering & computing
JID - 7704869
RN  - 0 (Transforming Growth Factor alpha)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques
MH  - Down-Regulation
MH  - Epidermal Growth Factor/*pharmacology
MH  - ErbB Receptors/*physiology
MH  - Humans
MH  - Mice
MH  - Mitosis/*physiology
MH  - Transforming Growth Factor alpha/*pharmacology
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - 10.1007/BF02523222 [doi]
PST - ppublish
SO  - Med Biol Eng Comput. 1998 Jul;36(4):499-507. doi: 10.1007/BF02523222.