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3 July 1997, Volume 15, Number 1, Pages 7-15
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Article
Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation
Masahiro Yokouchi1,2, Ritsu Suzuki1,2, Masaaki Masuhara1, Seturo Komiya2, Akio Inoue2 and Akihiko Yoshimura1,a

1Institute of Life Science, Kurume University, Aikawamachi 2432-3 Kurume 839, Japan

2Department of Orthopaedic Surgery, Faculty of Medicine, Kurume University, Aikawamachi 2432-3 Kurume 839, Japan

aAuthor for correspondence at: Institute of Life Science, Kurume University, Aikawamachi 2432-3 Kurume 839, Japan

Abstract

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation of a number of proteins, which leads to a cascade of biochemical changes that initiates B cell proliferation and differentiation or growth inhibition. A novel cDNA, designed APS, encoding an adaptor protein with a Pleckstrin homology (PH) domain, Src homology 2 (SH2) domain, and a tyrosine phosphorylation site was cloned from a B cell cDNA library using a yeast two hybrid system. APS is structurally similar to SH2-B, an SH2 protein that potentially binds to the immunoreceptor tyrosine-based activation motif (ITAM) as well as Lnk which is postulated to be a signal transducer that links T-cell receptor to phospholipase Cbold gamma, Grb2 and phosphatidylinositol 3-kinase. APS expressed only in human Burkitt's lymphoma cells among cell lines we examined and tyrosine phosphorylated in response to BCR stimulation. APS bound to Shc irrespective of stimulation and bound to Grb2 after stimulation, suggesting that it plays a role in linkage from BCR to Shc/Grb2 pathway. These results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune receptors to signaling pathways involved in tyrosine-phosphorylation.

Keywords

B lymphocytes; signal transduction; protein tyrosine kinase; SH2 domain; PH domain

Received 28 January 1999; revised 19 March 1999; accepted 20 March 1999
3 July 1997, Volume 15, Number 1, Pages 7-15
Table of contents    Previous  Abstract  Next   Article  PDF