Sm. Bradykalnay et al., RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE PTP-MU ASSOCIATES WITH CADHERINS AND CATENINS IN-VIVO, The Journal of cell biology, 130(4), 1995, pp. 977-986
The extracellular segment of the receptor-type protein tyrosine phosph
atase PTP mu, possesses an MAM domain, an immunoglobulin domain, and f
our fibronectin type-III repeats. It binds homophilically, i.e., PTP m
u on the surface of one cell binds to PTP mu on an apposing cell, and
the binding site lies within the immunoglobulin domain. The intracellu
lar segment of PTP mu has two PTP domains and a juxtamembrane segment
that is homologous to the conserved intracellular domain of the cadher
ins. In cadherins, this segment interacts with proteins termed catenin
s to mediate association with the actin cytoskeleton. In this article,
we demonstrate that PTP mu associates with a complex containing cadhe
rins, alpha- and beta-catenin in mink lung (MvLu) cells, and in rat he
art, lung, and brain tissues. Greater than 80% of the cadherin in the
cell is cleared from Triton X-100 lysates of MvLu cells after immuno-p
recipitation with antibodies to PTP mu; however, the complex is dissoc
iated when lysates are prepared in more stringent, SDS-containing RIPA
buffer. In vitro binding studies demonstrated that the intracellular
segment of PTP mu binds directly to the intracellular domain of E-cadh
erin, but not to alpha- or beta-catenin. Consistent with their ability
to interact in vivo, PTP mu, cadherins, and catenins all localized to
points of cell-cell contact in MvLu cells, as assessed by immunocytoc
hemical staining. After pervanadate treatment of MvLu cells, which inh
ibits cellular tyrosine phosphatase activity including PTP mu, the cad
herins associated with PTP mu are now found in a tyrosine-phosphorylat
ed form, indicating that the cadherins may be an endogenous substrate
for PTP mu. These data suggest that PTP mu may be one of the enzymes t
hat regulates the dynamic tyrosine phosphorylation, and thus function,
of the cadherin/catenin complex in vivo.