PMID- 10339428
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 10
DP  - 1999 May 20
TI  - Targeted disruption of the tyrosine phosphatase PTPalpha leads to constitutive
      downregulation of the kinases Src and Fyn.
PG  - 535-8
AB  - A role for the receptor-like protein tyrosine phosphatase alpha (PTPalpha) in
      regulating the kinase activity of Src family members has been proposed because
      ectopic expression of PTPalpha enhances the dephosphorylation and activation of
      Src and Fyn [1] [2] [3]. We have generated mice lacking catalytically active
      PTPalpha to address the question of whether PTPalpha is a physiological activator
      of Src and Fyn, and to investigate its other potential functions in the context
      of the whole animal. Mice homozygous for the targeted PTPalpha allele
      (PTPalpha-/-) and lacking detectable PTPalpha protein exhibited no gross
      phenotypic defects. The kinase activities of Src and Fyn were significantly
      reduced in PTPalpha-/- mouse brain and primary embryonic fibroblasts, and this
      correlated with enhanced phosphorylation of the carboxy-terminal regulatory
      Tyr527 of Src in PTPalpha-/- mice. Thus, PTPalpha is a physiological positive
      regulator of the tyrosine kinases Src and Fyn. Increased tyrosine phosphorylation
      of several unidentified proteins was also apparent in PTPalpha-/- mouse brain
      lysates. These may be PTPalpha substrates or downstream signaling proteins. Taken
      together, the results indicate that PTPalpha has a dual function as a positive
      and negative regulator of tyrosine phosphorylation events, increasing
      phosphotyrosyl proteins through activation of Src and Fyn, and directly or
      indirectly removing tyrosine phosphate from other unidentified proteins.
FAU - Ponniah, S
AU  - Ponniah S
AD  - Cell Regulation Laboratory, In Vivo Model Systems Unit, Institute of Molecular
      and Cell Biology, 30 Medical Drive, Singapore, 117609, Republic of Singapore.
FAU - Wang, D Z
AU  - Wang DZ
FAU - Lim, K L
AU  - Lim KL
FAU - Pallen, C J
AU  - Pallen CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - *Down-Regulation
MH  - Mice
MH  - Mutation
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatases/*genetics
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-fyn
MH  - src-Family Kinases/*metabolism
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - S0960-9822(99)80238-3 [pii]
AID - 10.1016/s0960-9822(99)80238-3 [doi]
PST - ppublish
SO  - Curr Biol. 1999 May 20;9(10):535-8. doi: 10.1016/s0960-9822(99)80238-3.