PMID- 10567341
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 48
DP  - 1999 Nov 26
TI  - Ndr protein kinase is regulated by phosphorylation on two conserved sequence 
      motifs.
PG  - 33847-50
AB  - Ndr is a nuclear serine/threonine protein kinase that belongs to a subfamily of 
      kinases implicated in the regulation of cell division and cell morphology. This 
      subfamily includes the kinases LATS, Orb6, Cot-1, and Dbf2. We show here that Ndr 
      is potently activated when intact cells are treated with okadaic acid, suggesting 
      that Ndr is normally held in a state of low activity by protein phosphatase 2A. 
      We mapped the regulatory phosphorylation sites of Ndr protein kinase and found 
      that active Ndr is phosphorylated on Ser-281 and Thr-444. Mutation of either site 
      to alanine strongly reduced both basal and okadaic acid-stimulated Ndr activity, 
      while combined mutation abolished Ndr activity completely. Importantly, each of 
      these sites (and also the surrounding sequences) are conserved in the kinase 
      relatives of Ndr, suggesting a general mechanism of activation for kinases of 
      this subfamily. Ser-281 and Thr-444 are also similar to the regulatory 
      phosphorylation sites in several targets of the phosphoinositide-dependent 
      protein kinase PDK1.(1) However, PDK1 does not appear to function as an upstream 
      kinase for Ndr. Thus, Ndr and its close relatives may operate in a novel 
      signaling pathway downstream of an as-yet-unidentified kinase with specificity 
      similar to, but distinct from, PDK1.
FAU - Millward, T A
AU  - Millward TA
AD  - Friedrich Miescher-Institut, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
FAU - Hess, D
AU  - Hess D
FAU - Hemmings, B A
AU  - Hemmings BA
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 (Nuclear Proteins)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Cell Line, Transformed
MH  - *Conserved Sequence
MH  - Humans
MH  - Mass Spectrometry/methods
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Sequence Analysis
MH  - Sequence Homology, Amino Acid
MH  - Serine/metabolism
MH  - Threonine/metabolism
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - S0021-9258(19)53468-8 [pii]
AID - 10.1074/jbc.274.48.33847 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 26;274(48):33847-50. doi: 10.1074/jbc.274.48.33847.