PMID- 10611247
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20220317
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Jan
TI  - Caspase 3 cleavage of the Ste20-related kinase SLK releases and activates an
      apoptosis-inducing kinase domain and an actin-disassembling region.
PG  - 684-96
AB  - We have demonstrated that a novel Ste20-related kinase, designated SLK, mediates 
      apoptosis and actin stress fiber dissolution through distinct domains generated
      by caspase 3 cleavage. Overexpression of SLK in C2C12 myoblasts stimulated the
      disassembly of actin stress fibers and focal adhesions and induced apoptosis, as 
      determined by annexin V binding and terminal deoxynucleotidyltransferase-mediated
      dUTP-biotin nick end labeling analysis. SLK was cleaved by caspase 3 in vitro and
      in vivo during c-Myc-, tumor necrosis factor alpha, and UV-induced apoptosis.
      Furthermore, cleavage of SLK released two domains with distinct activities: an
      activated N-terminal kinase domain that promoted apoptosis and cytoskeletal
      rearrangements and a C-terminus domain that disassembled actin stress fibers.
      Moreover, our analysis has identified a novel conserved region (termed the AT1-46
      homology domain) that efficiently promotes stress fiber disassembly. Finally,
      transient transfection of SLK also activated the c-Jun N-terminal kinase
      signaling pathway. Our results suggest that caspase-activated SLK represents a
      novel effector of cytoskeletal remodeling and apoptosis.
FAU - Sabourin, L A
AU  - Sabourin LA
AD  - Institute for Molecular Biology, McMaster University, Hamilton, Ontario, Canada.
FAU - Tamai, K
AU  - Tamai K
FAU - Seale, P
AU  - Seale P
FAU - Wagner, J
AU  - Wagner J
FAU - Rudnicki, M A
AU  - Rudnicki MA
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 (Actins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (SLK protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (SLK protein, mouse)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
EIN - Mol Cell Biol 2000 Apr;20(8):2949
MH  - Actins/*metabolism
MH  - Animals
MH  - *Apoptosis/drug effects/radiation effects
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - Cell Adhesion
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Cytoskeleton/drug effects/metabolism/radiation effects
MH  - Enzyme Activation/drug effects/radiation effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Muscles/cytology/enzymology/metabolism
MH  - Mutation/genetics
MH  - Protein Processing, Post-Translational/drug effects/radiation effects
MH  - Protein Serine-Threonine Kinases/*chemistry/genetics/*metabolism
MH  - Protein Structure, Tertiary/genetics/physiology
MH  - Proto-Oncogene Proteins c-myc/genetics/physiology
MH  - RNA, Messenger/analysis/genetics
MH  - Recombinant Fusion Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Two-Hybrid System Techniques
PMC - PMC85169
EDAT- 1999/12/28 09:00
MHDA- 2000/05/29 09:00
CRDT- 1999/12/28 09:00
PHST- 1999/12/28 09:00 [pubmed]
PHST- 2000/05/29 09:00 [medline]
PHST- 1999/12/28 09:00 [entrez]
AID - 10.1128/MCB.20.2.684-696.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Jan;20(2):684-96. doi: 10.1128/MCB.20.2.684-696.2000.