International Immunology, Vol 10, 1009-1016, Copyright © 1998 by Oxford University Press
PD King, A Sadra, JM Teng, GM Bell and B Dupont
Ligation of the CD2 co-stimulatory receptor on human T lymphocytes induces
tyrosine phosphorylation and activation of the Tec-family tyrosine kinase,
ITK. To examine whether any of several proline-rich (PR) stretches of the
CD2 cytoplasmic tail are necessary for ITK activation we introduced
wild-type and mutated versions of rat CD2, each missing at least one PR
stretch of the tail, into human Jurkat T leukemia cells. The influence of
cytoplasmic tail mutations was then studied following stimulation of
transfectants with the rat CD2 mAb pair, OX54/OX55. As predicted, wild-type
rat CD2 was able to activate ITK in Jurkat cells. In addition, a truncation
mutant, lacking the most membrane-distal PR stretch, PR6, was able to
activate ITK. By contrast, all other studied truncation mutants, each of
which is missing at least PR4-PR6, were unable to induce ITK activation. Of
deletion mutants, deletion of the membrane-proximal PR stretches, PR1-PR3,
did not impair rat CD2-mediated ITK activation. However, additional
deletion of PR4 from a tail missing PR1 and PR2, deletion of PR2 and PR4,
and deletion of PR4 alone from rat CD2 abrogated an ability to activate
ITK. Thus, these results identify PR4 as an element of the CD2 tail that is
required for activation of ITK. Furthermore, we show that, unlike wild-
type rat CD2, PR4-deleted rat CD2 is unable to induce IL-2 secretion from
Jurkat cells. This is consistent with the view that PR4-mediated activation
of ITK is important for downstream signaling events induced by CD2
co-stimulation.
ARTICLES
CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail
Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
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