Signaling through CD44 Is Mediated by Tyrosine Kinases

doi:10.1074/jbc.271.5.2863

Signaling through CD44 Is Mediated by Tyrosine Kinases

ASSOCIATION WITH p56 IN T LYMPHOCYTES (*)

From the (1)Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands and
(2)Department of Cellular Biochemistry, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands

^§To whom correspondence should be addressed:
Dept. of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
. Tel.: 31-20-5665635; Fax: 31-20-6960389.

Abstract

Evidence from a large body of studies indicates that CD44 is involved in a number of important biological processes, including lymphocyte activation and homing, hematopoiesis, and tumor progression and metastasis. A proper understanding of the role of CD44 in these processes has been severely hampered by a lack of insight into the mode in which CD44 communicates with intracellular signal transduction pathways. In this report, we have addressed this aspect of CD44 functioning by studying CD44 signaling in T lymphocytes. We show that ligation of CD44 by monoclonal antibodies (mAbs) transduces signals to T cells which lead to tyrosine phosphorylation of ZAP-70 and other intracellular proteins. In vitro kinase assays demonstrate that cross-linking of CD44 induces an increase in the intrinsic activity of p56. Furthermore, immunoprecipitations show that CD44 is physically associated with p56. Our findings suggest that tyrosine kinases, particularly p56, play a central role in CD44 mediated signaling.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

TCR

T cell receptor

mAb

monoclonal antibody

HRP

horseradish peroxidase

PAGE

polyacrylamide gel electrophoresis

PY

phosphotyrosine

GαM

goat anti-mouse Ig

T-PBL

peripheral blood T lymphocyte.
- Received September 1, 1995.
- Revision received November 20, 1995.