PMID- 9089656
OWN - NLM
STAT- MEDLINE
DCOM- 19970603
LR  - 20190813
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 126
IP  - 2
DP  - 1997 Feb 7
TI  - Intraendosomal degradation of transforming growth factor alpha.
PG  - 185-92
AB  - Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) 
      bind to the same receptor, but have different potencies and actions. A possible 
      mechanism is that differences in processing may be responsible for their 
      divergent properties. We have examined TGF alpha and EGF processing in isolated 
      rat hepatocytes with and without various protease inhibitors and inhibitors of 
      endosomal processing. Our results show that EGF undergoes limited degradation in 
      endosomes and is primarily degraded in lysosomes. In contrast, TGF alpha is 
      rapidly degraded in endosomes by insulin-degrading enzyme (EC 3.4.24.56), 
      possibly allowing rapid return of the receptor to the cell surface. Incubation of 
      isolated endosomes preloaded with labeled TGF alpha reveals that degradation can 
      occur whether the vesicles are acidified or not, as is also the case for insulin. 
      We conclude that TGF alpha is degraded immediately after internalization, at 
      least partly before acidification has occurred, while EGF requires prolonged 
      intracellular residence and lysosomal degradation. The different degradation 
      pathways may play a role in the different activities of the two hormones.
FAU - Hamel, F G
AU  - Hamel FG
AD  - Research Service, Department of Veterans Affairs Medical Center-R151, Omaha, NE 
      68105, USA.
FAU - Siford, G L
AU  - Siford GL
FAU - Jones, J
AU  - Jones J
FAU - Duckworth, W C
AU  - Duckworth WC
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Transforming Growth Factor alpha)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Endosomes/*metabolism
MH  - Epidermal Growth Factor/*metabolism
MH  - Liver/*metabolism/ultrastructure
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transforming Growth Factor alpha/*metabolism
EDAT- 1997/02/07 00:00
MHDA- 1997/02/07 00:01
CRDT- 1997/02/07 00:00
PHST- 1997/02/07 00:00 [pubmed]
PHST- 1997/02/07 00:01 [medline]
PHST- 1997/02/07 00:00 [entrez]
AID - S0303-7207(96)03981-0 [pii]
AID - 10.1016/s0303-7207(96)03981-0 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 1997 Feb 7;126(2):185-92. doi: 
      10.1016/s0303-7207(96)03981-0.