Limits...
The Emerging and Diverse Roles of Src-Like Adaptor Proteins in Health and Disease.

Marton N, Baricza E, Érsek B, Buzás EI, Nagy G - Mediators Inflamm. (2015)

Bottom Line: Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered.Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways.In this review, we summarize the diverse effects of SLAP proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, 4 Nagyvárad Square, Budapest 1089, Hungary.

ABSTRACT
Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered. In addition to the well-characterized immunoregulatory functions, SLAP proteins appear to have an essential role in the pathogenesis of type I hypersensitivity, osteoporosis, and numerous malignant diseases. Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways. In this review, we summarize the diverse effects of SLAP proteins.

No MeSH data available.


Related in: MedlinePlus

The role of SLAP in T lymphocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4539169&req=5

fig3: The role of SLAP in T lymphocytes.

Mentions: SLAP-1 reduces the production of IL-2 and the transcription of NFATc1 and AP-1, thereafter functions as a negative regulator of the TCR signaling; both SH2 and SH3 domains are necessary for this effect. However, upon ionomycin or PMA activation of lymphocytes, these inhibitory effects are absent suggesting that SLAP-1 regulates the proximal part of the TCR pathway [7]. SLAP may associate with the N-terminal of the E3 ubiquitin ligase c-Cbl in a tyrosine phosphorylation independent way [16]. The simultaneous expression of SLAP-1 and c-Cbl promotes the ubiquitination and degradation of the ζ-chain, consequently enhancing the recycling and preventing the accumulation of the receptor complexes [17]. By contrast, similarly to SLAP −/− lymphocytes, c-Cbl −/− lymphocytes overexpress the ζ-chain due to its abolished degradation [18]. For successful operation, SLAP-1 requires the phosphorylation of the cytoplasmic domains of the TCR ζ-chains and the activation of Lck, but not of ZAP70 [19]. It has been shown that the phosphorylated proportion of the ζ-chains is slightly traceable in Lck −/− lymphocytes [20, 21]. SLAP colocalizes with early endosomes according to confocal microscopy images [7] (Figure 3). It is noteworthy that downregulation of ζ-chain of T-cells has been observed in many pathological conditions including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV) infection, and various cancers [22–28].


The Emerging and Diverse Roles of Src-Like Adaptor Proteins in Health and Disease.

Marton N, Baricza E, Érsek B, Buzás EI, Nagy G - Mediators Inflamm. (2015)

The role of SLAP in T lymphocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539169&req=5

fig3: The role of SLAP in T lymphocytes.
Mentions: SLAP-1 reduces the production of IL-2 and the transcription of NFATc1 and AP-1, thereafter functions as a negative regulator of the TCR signaling; both SH2 and SH3 domains are necessary for this effect. However, upon ionomycin or PMA activation of lymphocytes, these inhibitory effects are absent suggesting that SLAP-1 regulates the proximal part of the TCR pathway [7]. SLAP may associate with the N-terminal of the E3 ubiquitin ligase c-Cbl in a tyrosine phosphorylation independent way [16]. The simultaneous expression of SLAP-1 and c-Cbl promotes the ubiquitination and degradation of the ζ-chain, consequently enhancing the recycling and preventing the accumulation of the receptor complexes [17]. By contrast, similarly to SLAP −/− lymphocytes, c-Cbl −/− lymphocytes overexpress the ζ-chain due to its abolished degradation [18]. For successful operation, SLAP-1 requires the phosphorylation of the cytoplasmic domains of the TCR ζ-chains and the activation of Lck, but not of ZAP70 [19]. It has been shown that the phosphorylated proportion of the ζ-chains is slightly traceable in Lck −/− lymphocytes [20, 21]. SLAP colocalizes with early endosomes according to confocal microscopy images [7] (Figure 3). It is noteworthy that downregulation of ζ-chain of T-cells has been observed in many pathological conditions including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV) infection, and various cancers [22–28].

Bottom Line: Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered.Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways.In this review, we summarize the diverse effects of SLAP proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, 4 Nagyvárad Square, Budapest 1089, Hungary.

ABSTRACT
Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered. In addition to the well-characterized immunoregulatory functions, SLAP proteins appear to have an essential role in the pathogenesis of type I hypersensitivity, osteoporosis, and numerous malignant diseases. Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways. In this review, we summarize the diverse effects of SLAP proteins.

No MeSH data available.


Related in: MedlinePlus