PMID- 7844156
OWN - NLM
STAT- MEDLINE
DCOM- 19950306
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 128
IP  - 3
DP  - 1995 Feb
TI  - Transforming growth factor-alpha and beta-amyloid precursor protein share a 
      secretory mechanism.
PG  - 433-41
AB  - Cleavage and release of membrane protein ectodomains, a regulated process that 
      affects many cell surface proteins, remains largely uncharacterized. To 
      investigate whether cell surface proteins are cleaved through a shared mechanism 
      or through multiple independent mechanisms, we mutagenized Chinese hamster ovary 
      (CHO) cells and selected clones that were unable to cleave membrane-anchored 
      transforming growth factor alpha (TGF-alpha). The defect in TGF-alpha cleavage in 
      these clones is most apparent upon cell treatment with the protein kinase C (PKC) 
      activator PMA, which stimulates TGF-alpha cleavage in wild-type cells. The mutant 
      clones do not have defects in TFG-alpha expression, transport to the cell surface 
      or turnover. Concomitant with the loss of TGF-alpha cleavage, these clones have 
      lost the ability to cleave many structurally unrelated membrane proteins in 
      response to PMA. These proteins include beta-amyloid precursor protein 
      (beta-APP), whose cleavage into a secreted form avoids conversion into the 
      amyloidogenic peptide A beta, and a group of cell surface proteins whose release 
      into the medium is stimulated by PMA in wild type CHO cells but not in mutants. 
      The mutations prevent cleavage by PKC-dependent as well as PKC-independent 
      mechanisms, and thus affect an essential component that functions downstream of 
      these various signaling mechanisms. We propose that regulated cleavage and 
      secretion of membrane protein ectodomains is mediated by a common system whose 
      components respond to multiple activators and act on susceptible proteins of 
      diverse structure and function.
FAU - Arribas, J
AU  - Arribas J
AD  - Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New 
      York 10021.
FAU - Massague, J
AU  - Massague J
LA  - eng
GR  - CA53559/CA/NCI 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 Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Transforming Growth Factor alpha)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amyloid beta-Protein Precursor/biosynthesis/*metabolism/physiology
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - CHO Cells
MH  - Cricetinae
MH  - Hydrolysis
MH  - Membrane Proteins/metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oligodeoxyribonucleotides
MH  - Rats
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transforming Growth Factor alpha/biosynthesis/*metabolism/physiology
PMC - PMC2120346
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
PMCR- 1995/08/01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PHST- 1995/08/01 00:00 [pmc-release]
AID - 95146549 [pii]
AID - 10.1083/jcb.128.3.433 [doi]
PST - ppublish
SO  - J Cell Biol. 1995 Feb;128(3):433-41. doi: 10.1083/jcb.128.3.433.