PMID- 10915792
OWN - NLM
STAT- MEDLINE
DCOM- 20001113
LR  - 20220314
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 41
DP  - 2000 Oct 13
TI  - Identification of a common protein association region in the neuronal Cdk5 
      activator.
PG  - 31763-9
AB  - Cyclin-dependent protein kinase 5 (Cdk5) depends on the association with neuronal 
      Cdk5 activator (Nck5a) for kinase activity. A variety of cellular proteins have 
      been shown to undergo high affinity association with Nck5a, including three novel 
      proteins, C42, C48, and C53 found by a yeast two-hybrid screen (Ching, Y. P., Qi, 
      Z., and Wang, J. H. (2000) Gene 242, 285-294). The three proteins show 
      competitive binding to Nck5a suggesting that they bind at a common site. The 
      binding site has been mapped to a region of 26 amino acid residues (residues 145 
      to 170) at the N-terminal boundary of the kinase activation domain of Nck5a. This 
      region of Nck5a contains an amphipathic alpha-helix whose hydrophobic face is 
      involved in Cdk5 activation (Chin, K. T., Ohki, S, Tang, D., Cheng, H. C., Wang, 
      J. H. , and Zhang, M. (1999) J. Biol. Chem. 274, 7120-7127). Several lines of 
      evidence suggest that Nck5a interacts with the binding proteins at the 
      hydrophilic face of the amphipathic alpha-helix. First, the Nck5a-(145-170) 
      peptide can bind Cdk5 and Nck5a-binding proteins simultaneously. Second, the 
      association of Nck5a-(145-170) to C48 can be markedly reduced by high ionic 
      strength whereas the interaction between Nck5a and Cdk5 is not affected. Third, 
      substitution of Glu(157) by glutamine in Nck5a-(145-170) abolishes the peptide's 
      ability to bind to the three Nck5a-binding proteins without diminishing its Cdk5 
      binding activity.
FAU - Wang, X
AU  - Wang X
AD  - Department of Biochemistry, The Hong Kong University of Science and Technology, 
      Clear Water Bay, Kowloon, Hong Kong, Peoples Republic of China.
FAU - Ching, Y P
AU  - Ching YP
FAU - Lam, W H
AU  - Lam WH
FAU - Qi, Z
AU  - Qi Z
FAU - Zhang, M
AU  - Zhang M
FAU - Wang, J H
AU  - Wang JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CDK5RAP2 protein, human)
RN  - 0 (CDK5RAP3 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (neuronal Cdk5 activator (p25-p35))
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (CDK5 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 2.8.- (CDK5RAP1 protein, human)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Binding, Competitive
MH  - Carrier Proteins/*metabolism
MH  - Cell Cycle Proteins
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Macromolecular Substances
MH  - Mutation/genetics
MH  - Nerve Tissue Proteins/*chemistry/genetics/*metabolism
MH  - Osmolar Concentration
MH  - Peptide Fragments/metabolism
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Recombinant Fusion Proteins/metabolism
MH  - Tumor Suppressor Proteins
EDAT- 2000/08/01 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/01 11:00
PHST- 2000/08/01 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/01 11:00 [entrez]
AID - S0021-9258(20)89250-3 [pii]
AID - 10.1074/jbc.M004358200 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Oct 13;275(41):31763-9. doi: 10.1074/jbc.M004358200.