PMID- 8570096
OWN - NLM
STAT- MEDLINE
DCOM- 19960301
LR  - 20190701
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 198
IP  - 1
DP  - 1995 Sep 22
TI  - Amino-terminal region of the beta-amyloid precursor protein activates 
      mitogen-activated protein kinase.
PG  - 52-6
AB  - The secreted form of the beta-amyloid precursor protein (beta-APP) has previously 
      been shown to stimulate mitogen-activated protein (MAP) kinases in PC-12 
      pheochromocytoma cells. The amino-terminal half of secreted beta-APP contains a 
      region rich in cysteine residues reminiscent of cysteine-rich binding regions in 
      other families of extracellular proteins. We found that reductive alkylation of 
      disulfide linkages eliminated the ability of secreted beta-APP to activate MAP 
      kinase. To confirm the role of the cysteine-rich amino-terminal region, fragments 
      representing the amino- and carboxyl-terminal halves of secreted beta-APP were 
      expressed in bacteria as fusion proteins and purified. Ten-minute treatment with 
      the amino-terminal segment of beta-APP activated MAP kinase approximately 
      15-fold, while the carboxyl segment had no effect. The amino-terminal fragment, 
      like intact secreted beta-APP, was substantially inactivated by reduction of 
      sulfhydryl groups. These results suggest that the amino-terminal region of 
      beta-APP is responsible for activation of MAP kinase and that it requires 
      structural loops created by disulfide linkages for activity.
FAU - Greenberg, S M
AU  - Greenberg SM
AD  - Department of Neurology, Harvard Medical School, Brigham and Women's Hospital, 
      Boston, MA 02115, USA.
FAU - Qiu, W Q
AU  - Qiu WQ
FAU - Selkoe, D J
AU  - Selkoe DJ
FAU - Ben-Itzhak, A
AU  - Ben-Itzhak A
FAU - Kosik, K S
AU  - Kosik KS
LA  - eng
GR  - AG06601/AG/NIA 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  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Disulfides)
RN  - 0 (Mitogens)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Alkylation
MH  - Amino Acid Sequence
MH  - Amyloid beta-Protein Precursor/*physiology
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cricetinae
MH  - Disulfides/metabolism
MH  - Enzyme Activation/drug effects
MH  - Mitogens/*pharmacology
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - PC12 Cells
MH  - Rats
EDAT- 1995/09/22 00:00
MHDA- 1995/09/22 00:01
CRDT- 1995/09/22 00:00
PHST- 1995/09/22 00:00 [pubmed]
PHST- 1995/09/22 00:01 [medline]
PHST- 1995/09/22 00:00 [entrez]
AID - 0304-3940(95)11944-R [pii]
AID - 10.1016/0304-3940(95)11944-r [doi]
PST - ppublish
SO  - Neurosci Lett. 1995 Sep 22;198(1):52-6. doi: 10.1016/0304-3940(95)11944-r.