PMID- 8702870
OWN - NLM
STAT- MEDLINE
DCOM- 19961010
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 35
DP  - 1996 Aug 30
TI  - The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain.
PG  - 21049-53
AB  - The human serine/threonine protein kinases, Mst1 and Mst2, share considerable 
      homology to Ste20 and p21-activated kinase (Pak) throughout their catalytic 
      domains. However, outside the catalytic domains there are no significant 
      homologies to previously described Ste20-like kinases or other proteins. To 
      understand the role of the nonhomologous regions, we performed a 
      structure/function analysis of Mst1. A series of COOH-terminal and internal 
      deletions indicates that there is an element within a central 63-amino acid 
      region of the molecule that inhibits kinase activity. Removal of this domain 
      increases kinase activity approximately 9-fold. Coimmunoprecipitation assays, the 
      yeast two-hybrid procedure, and in vitro cross-linking analysis indicate that 
      Mst1 homodimerizes and that the extreme COOH-terminal 57 amino acids are required 
      for self-association. Size exclusion chromatography indicates that Mst1 is 
      associated with a high molecular weight complex in cells, suggesting that other 
      proteins may also oligomerize with this kinase. While loss of dimerization alone 
      does not affect kinase activity, a molecule lacking both the dimerization and 
      inhibitory domains is not as active as one which lacks only the inhibitory 
      domain. Comparison of Mst1 and Mst2 indicates that both functional domains lie in 
      regions conserved between the two molecules.
FAU - Creasy, C L
AU  - Creasy CL
AD  - Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
FAU - Ambrose, D M
AU  - Ambrose DM
FAU - Chernoff, J
AU  - Chernoff J
LA  - eng
GR  - CA-06927/CA/NCI NIH HHS/United States
GR  - CA-09035/CA/NCI NIH HHS/United States
GR  - R01 CA58836/CA/NCI 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  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Biopolymers)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (DNA Primers)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - EC 2.7.1.11 (STK4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - T3C89M417N (Glutaral)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biopolymers
MH  - Catalysis
MH  - Cell Line
MH  - Cross-Linking Reagents/chemistry
MH  - DNA Primers
MH  - Glutaral/chemistry
MH  - Intracellular Signaling Peptides and Proteins
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Monosaccharide Transport Proteins/antagonists & inhibitors/chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/chemistry/*metabolism
MH  - Saccharomyces cerevisiae/enzymology
MH  - Structure-Activity Relationship
EDAT- 1996/08/30 00:00
MHDA- 1996/08/30 00:01
CRDT- 1996/08/30 00:00
PHST- 1996/08/30 00:00 [pubmed]
PHST- 1996/08/30 00:01 [medline]
PHST- 1996/08/30 00:00 [entrez]
AID - S0021-9258(19)74613-4 [pii]
AID - 10.1074/jbc.271.35.21049 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Aug 30;271(35):21049-53. doi: 10.1074/jbc.271.35.21049.