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Critical Reviews™ in Immunology

Impact factor: 3.857

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v26.i5.20
pages 391-406

Structure and Function of Cas-L and Integrin-Mediated Signaling

Sachiko Seo
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Motoshi Ichikawa
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Mineo Kurokawa
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

ABSTRACT

Cas-L (Crk-associated substrate lymphocyte type), also known as HEF1 (human enhancer of filamentation 1) or NEDD9 (neural precursor cell-expressed, developmentally downregulated gene 9), is an adapter protein at focal adhesions and transmits various signals, mainly induced by integrins. Cas-L is a member of the Cas family proteins and is expressed preferentially in lymphocytes and epithelial cells. A number of previous studies have suggested that Cas-L plays an important role in lymphocyte movement and cell cycle. Recently, we reported a novel function of Cas-L in the immune system using gene-targeted mice. The Cas-L-deficient lymphocytes showed insufficient chemotactic response and perturbed сеll adhesion. Moreover, a deficit of marginal zone (MZ) B cells was detected in the mutant mice. Here, we review the structure of Cas-L and several signaling pathways in which Cas-L is involved, based on the previous in vitro studies. Subsequently, biological functions of Cas-L and the relevance of Cas-L to human diseases are discussed.