PMID- 10364224
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the 
      band 4.1-related protein-tyrosine phosphatase PTPH1.
PG  - 17806-12
AB  - The human band 4.1-related protein-tyrosine phosphatase PTPH1 was introduced into
      NIH3T3 cells under the control of a tetracycline-repressible promoter. Ectopic
      expression of wild type PTPH1 dramatically inhibited cell growth, whereas a
      catalytically impaired mutant showed no effect. To identify the direct target of 
      PTPH1 in the cell, we generated a substrate-trapping mutant, in which an
      invariant aspartate residue was changed to alanine (D811A in PTPH1). The
      PTPH1-D811A mutant trapped primarily a 97-kDa tyrosine-phosphorylated protein,
      which was determined to be VCP (also named p97 or yeast CDC48), from various cell
      lysates in vitro. However, when expressed in mammalian cells, the D811A mutant
      was observed to contain high levels of phosphotyrosine and did not trap
      substrates. Mutation of tyrosine 676 to phenylalanine (Y676F) in the PTPH1-D811A 
      mutant led to a marked reduction in phosphotyrosine content. Furthermore, this
      double mutant specifically trapped VCP in vivo and recognized the C-terminal
      tyrosines of VCP, whose phosphorylation is important for cell cycle progression
      in yeast. Like wild type PTPH1, this double mutant also inhibited cell
      proliferation. Moreover, induction of wild type PTPH1 resulted in specific
      dephosphorylation of VCP without changing the overall phosphotyrosine profile of 
      the cells. VCP has been implicated in control of a variety of membrane functions,
      including membrane fusions, and is a regulator of the cell cycle. Our results
      suggest that PTPH1 may exert its effects on cell growth through dephosphorylation
      of VCP, thus implicating tyrosine phosphorylation as an important regulator of
      VCP function.
FAU - Zhang, S H
AU  - Zhang SH
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
FAU - Liu, J
AU  - Liu J
FAU - Kobayashi, R
AU  - Kobayashi R
FAU - Tonks, N K
AU  - Tonks NK
LA  - eng
GR  - CA53840/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 (Cell Cycle Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 3.1.3.48 (PTPN3 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 3)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn3 protein, mouse)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.4.6 (VCP protein, human)
RN  - EC 3.6.4.6 (Valosin Containing Protein)
RN  - EC 3.6.4.6 (Vcp protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - Adenosine Triphosphatases
MH  - Animals
MH  - Cell Cycle/*genetics
MH  - Cell Cycle Proteins/*metabolism
MH  - Cell Division
MH  - Cell Line
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Mice
MH  - Mutation
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 3
MH  - Protein Tyrosine Phosphatases/genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Valosin Containing Protein
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.17806 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):17806-12. doi: 10.1074/jbc.274.25.17806.