TYROSINE PHOSPHORYLATION IF CD45 PHOSPHOTYROSINE PHOSPHATASE BY P50(CSK) KINASE CREATES A BINDING-SITE FOR P56(LCK) TYROSINE KINASE AND ACTIVATES THE PHOSPHATASE
M. Autero et al., TYROSINE PHOSPHORYLATION IF CD45 PHOSPHOTYROSINE PHOSPHATASE BY P50(CSK) KINASE CREATES A BINDING-SITE FOR P56(LCK) TYROSINE KINASE AND ACTIVATES THE PHOSPHATASE, Molecular and cellular biology, 14(2), 1994, pp. 1308-1321
Src family protein tyrosine kinases (PTKs) play an essential role in a
ntigen receptor-initiated lymphocyte activation. Their activity is lar
gely regulated by a negative regulatory tyrosine which is a substrate
for the activating action of the CD45 phosphotyrosine phosphatase (PTP
ase) or, conversely, the suppressing action of the cytosolic p50(csk)
PTK. Here we report that CD45 was phosphorylated by p50(csk) on two ty
rosine residues, one of them identified as Tyr-1193. This residue was
not phosphorylated by T-cell PTKs p56(lck) and p59(fyn). Tyr-1193 was
phosphorylated in intact T cells, and phosphorylation increased upon t
reatment with PTPase inhibitors, indicating that this tyrosine is a ta
rget for a constitutively active PTK. Cotransfection of CD45 and csk i
nto COS-1 cells caused tyrosine phosphorylation of CD45 in the intact
cells. Tyrosine-phosphorylated CD45 bound p56(lck) through the SH2 dom
ain of the kinase. Finally, p50(csk)-mediated phosphorylation of CD45
caused a severalfold increase in its PTPase activity. Our results show
that direct tyrosine phosphorylation of CD45 can affect its activity
and association with Src family PTKs and that this phosphorylation cou
ld be mediated by p50(csk). If this is also true in the intact cells,
it adds a new dimension to the physiological function of p50(csk) in T
lymphocytes.