SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking.
Src-like adapter proteins (SLAP and SLAP-2) constitute a family of proteins that are expressed in a variety of cell types but are studied most extensively in lymphocytes. They have been shown to associate with proximal components of the T-cell receptor (TCR) and B-cell receptor (BCR) signaling complexes. An interaction of SLAP with c-Cbl leads to the ubiquitination and degradation of phosphorylated components of the TCR- and BCR-signaling complexes. The absence of this process in immature SLAP-deficient T and B cells leads to increased immunoreceptor levels due to decreased intracellular retention and degradation. We propose a model in which SLAP-dependent regulation of immunoreceptor levels allows for finer control of immunoreceptor signaling. Thus, SLAP functions to dampen immunoreceptor signaling, thereby influencing lymphocyte development and repertoire selection.
Dragone
Leonard L
LL
National Jewish Health, Denver, CO 80206, USA. dragonel@njhealth.org
Shaw
Laura A
LA
Myers
Margaret D
MD
Weiss
Arthur
A
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000276:immunology / Q000378:metabolism*; D011946:Receptors, Antigen / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054875:Ubiquitination / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D011946:Receptors, Antigen; C490635:SLA protein, human; D050721:Proto-Oncogene Proteins c-cbl; D016392:Proto-Oncogene Proteins pp60(c-src)