PMID- 10629061
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 3
DP  - 2000 Feb
TI  - Death-associated protein kinase-related protein 1, a novel serine/threonine
      kinase involved in apoptosis.
PG  - 1044-54
AB  - In this study we describe the identification and structure-function analysis of a
      novel death-associated protein (DAP) kinase-related protein, DRP-1. DRP-1 is a
      42-kDa Ca(2+)/calmodulin (CaM)-regulated serine threonine kinase which shows high
      degree of homology to DAP kinase. The region of homology spans the catalytic
      domain and the CaM-regulatory region, whereas the remaining C-terminal part of
      the protein differs completely from DAP kinase and displays no homology to any
      known protein. The catalytic domain is also homologous to the recently identified
      ZIP kinase and to a lesser extent to the catalytic domains of DRAK1 and -2. Thus,
      DAP kinase DRP-1, ZIP kinase, and DRAK1/2 together form a novel subfamily of
      serine/threonine kinases. DRP-1 is localized to the cytoplasm, as shown by
      immunostaining and cellular fractionation assays. It binds to CaM, undergoes
      autophosphorylation, and phosphorylates an exogenous substrate, the myosin light 
      chain, in a Ca(2+)/CaM-dependent manner. The truncated protein, deleted of the
      CaM-regulatory domain, was converted into a constitutively active kinase.
      Ectopically expressed DRP-1 induced apoptosis in various types of cells. Cell
      killing by DRP-1 was dependent on two features: the status of the catalytic
      activity, and the presence of the C-terminal 40 amino acids shown to be required 
      for self-dimerization of the kinase. Interestingly, further deletion of the
      CaM-regulatory region could override the indispensable role of the C-terminal
      tail in apoptosis and generated a "superkiller" mutant. A dominant negative
      fragment of DAP kinase encompassing the death domain was found to block apoptosis
      induced by DRP-1. Conversely, a catalytically inactive mutant of DRP-1, which
      functioned in a dominant negative manner, was significantly less effective in
      blocking cell death induced by DAP kinase. Possible functional connections
      between DAP kinase and DRP-1 are discussed.
FAU - Inbal, B
AU  - Inbal B
AD  - Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100,
      Israel.
FAU - Shani, G
AU  - Shani G
FAU - Cohen, O
AU  - Cohen O
FAU - Kissil, J L
AU  - Kissil JL
FAU - Kimchi, A
AU  - Kimchi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK17A protein, human)
RN  - EC 2.7.11.1 (STK17B protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Base Sequence
MH  - Breast Neoplasms
MH  - Calcium-Calmodulin-Dependent Protein Kinases
MH  - Catalytic Domain
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Death-Associated Protein Kinases
MH  - Female
MH  - Gene Library
MH  - Humans
MH  - Kidney
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - Protein Biosynthesis
MH  - Protein-Serine-Threonine Kinases/*chemistry/*genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Spleen/metabolism
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
PMC - PMC85221
EDAT- 2000/01/11 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/11 09:00
PHST- 2000/01/11 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/11 09:00 [entrez]
AID - 10.1128/mcb.20.3.1044-1054.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Feb;20(3):1044-54. doi: 10.1128/mcb.20.3.1044-1054.2000.