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Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase.

Abstract：

:ZAP-70 and Syk are PTKs required for TCR and BCR function, respectively. Loss of the Syk PTK results in a nonfunctional BCR. We provide evidence here that ZAP-70 and Syk are functionally homologous in antigen receptor signaling by demonstrating that expression of ZAP-70 in Syk- B cells reconstitutes BCR function. Reconstitution required the presence of functional Src homology 2 (SH2) and catalytic domains of ZAP-70. Thus, drug targeting of a single SH2 domain within ZAP-70 should be sufficient to inhibit hematopoietic antigen receptor function. In addition, we demonstrate that both ZAP-70 and Syk can bind directly to the phosphorylated Ig alpha and Ig beta subunits with affinities comparable to their binding to the TCR CD3 epsilon subunit. These data suggest that ZAP-70 and Syk are comparable in their abilities to mediate hematopoietic antigen receptor signaling.

journal_name

Immunity

journal_title

Immunity

authors

Kong GH,Bu JY,Kurosaki T,Shaw AS,Chan AC

doi

10.1016/1074-7613(95)90029-2

subject

Has Abstract

pub_date

1995-05-01 00:00:00

pages

485-92

issue

5

eissn

1074-7613

issn

1097-4180

pii

1074-7613(95)90029-2

journal_volume

2

pub_type

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