PMID- 10574929
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 49
DP  - 1999 Dec 3
TI  - The novel kinase peptidylglycine alpha-amidating monooxygenase cytosolic
      interactor protein 2 interacts with the cytosolic routing determinants of the
      peptide processing enzyme peptidylglycine alpha-amidating monooxygenase.
PG  - 34646-56
AB  - The cytosolic domain of the peptide-processing integral membrane protein
      peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14. 17.3) contains
      multiple signals determining its subcellular localization. Three PAM cytosolic
      interactor proteins (P-CIPs) were identified using the yeast two hybrid system
      (Alam, M. R., Caldwel, B. D., Johnson, R. C., Darlington, D. N., Mains, R. E.,
      and Eipper, B. A. (1996) J. Biol. Chem. 271, 28636-28640); the partial amino acid
      sequence of P-CIP2 suggested that it was a protein kinase. In situ hybridization 
      and immunocytochemistry show that P-CIP2 is expressed widely throughout the
      brain; PAM and P-CIP2 are expressed in the same neurons. Based on subcellular
      fractionation, the 47-kDa P-CIP2 protein is mostly cytosolic. P-CIP2 is a highly 
      selective kinase, phosphorylating the cytosolic domain of PAM, but not the
      corresponding region of furin or carboxypeptidase D. Although P-CIP2 interacts
      with stathmin, it does not phosphorylate stathmin. Site-directed mutagenesis,
      phosphoamino acid analysis, and use of synthetic peptides demonstrate that
      PAM-Ser(949) is the major site phosphorylated by P-CIP2. Based on both in vitro
      binding experiments and co-immunoprecipitation from cell extracts, P-CIP2
      interacts with PAM proteins containing the wild type cytosolic domain, but not
      with mutant forms of PAM whose trafficking is disrupted. P-CIP2, through its
      highly selective phosphorylation of a key site in the cytosolic domain of PAM,
      appears to play a critical role in the trafficking of this protein.
FAU - Caldwell, B D
AU  - Caldwell BD
AD  - Department of Neuroscience, The Johns Hopkins University School of Medicine,
      Baltimore Maryland 21205, USA.
FAU - Darlington, D N
AU  - Darlington DN
FAU - Penzes, P
AU  - Penzes P
FAU - Johnson, R C
AU  - Johnson RC
FAU - Eipper, B A
AU  - Eipper BA
FAU - Mains, R E
AU  - Mains RE
LA  - eng
GR  - DK-32949/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Uhmk1 protein, rat)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.17.3 (peptidylglycine monooxygenase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Brain/enzymology
MH  - COS Cells
MH  - Carrier Proteins/genetics/*metabolism
MH  - Catalysis
MH  - *Cyclic AMP-Dependent Protein Kinases
MH  - Cytosol/*enzymology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mixed Function Oxygenases/*metabolism
MH  - Molecular Sequence Data
MH  - *Multienzyme Complexes
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases
MH  - Rats
MH  - Recombinant Fusion Proteins/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
MH  - Tissue Distribution
MH  - Tumor Cells, Cultured
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - 10.1074/jbc.274.49.34646 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 3;274(49):34646-56. doi: 10.1074/jbc.274.49.34646.