PubMed Journals: J Biol Chem
Source: PMID: 10574931
⇦ ⇨ J Biol Chem. 1999 Dec 3;274(49):34663-8.
Functional interaction between SHPTP1 and
the Lyn tyrosine kinase in the apoptotic
response to DNA damage.
Yoshida K(1), Kharbanda S, Kufe D.
(1) Dana-Farber Cancer Institute,
Harvard Medical School, Boston, Massachusetts
The Lyn protein-tyrosine kinase is activated
in the cellular response to DNA-damaging agents.
Here we demonstrate that Lyn associates
constitutively with the SHPTP1 protein-tyrosine
phosphatase. The SH3 domain of Lyn interacts
directly with SHPTP1. The results show that
Lyn phosphorylates SHPTP1 at the C-terminal Tyr-564
site. Lyn-mediated phosphorylation of SHPTP1
stimulates SHPTP1 tyrosine phosphatase activity.
We also demonstrate that treatment of cells
with 1-beta-D-arabinofuranosylcytosine and
other genotoxic agents induces Lyn-dependent
phosphorylation and activation of SHPTP1.
The significance of the Lyn-SHPTP1 interaction
is supported by the demonstration that activation
of Lyn contributes in part to the apoptotic
response to ara-C treatment and that SHPTP1
attenuates this response. These findings
support a functional interaction between
Lyn and SHPTP1 in the response to DNA damage.
PMID: 10574931 [Indexed for MEDLINE]