Disease relevance of SYK

• The phosphorylation of SYK is blocked by pertussis toxin, implicating a Gi-like heterotrimeric G protein [1].
• Although SYK has not been linked to a human disease, defective expression of the closely related T-cell tyrosine kinase ZAP-70 has been associated with severe combined immunodeficiency [2].
• In all nine T-ALL samples studied, the leukaemic cells showed a marked reduction in the expression of the zeta chain, while a variety of tyrosine kinases (p56lck, ZAP70 and SYK) were normally present [3].
• Squamous cell carcinomas revealed a peak incidence of hypermethylation of the 14-3-3 sigma gene (80%), and conversely, the lowest methylation frequency of the SYK gene (13.3%) [4].
• Undifferentiated small cell carcinomas disclosed a promoter methylation of the 14-3-3 sigma, SYK and CAGE-1 genes in only a quarter each for the cases [4].

High impact information on SYK

• Investigating possible interference of BCR-ABL1 with pre-B cell receptor signaling, we found that neither SYK nor SLP65 can be phosphorylated in response to pre-B cell receptor engagement [5].
• Tyrosine kinase SYK: essential functions for immunoreceptor signalling [6].
• Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein [7].
• Using bisulfite genomic sequencing we found that in microdissected HRS cells of primary cHL SYK, BOB.1/OBF.1, and CD79B promoters were also hypermethylated [8].
• Importantly, leukocyte rolling on P-selectin induced the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase associated to lipid raft PSGL-1 [9].

Chemical compound and disease context of SYK

• In our study, we explored the possibility of using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (AZA), to suppress breast cancer cell invasion by restoring SYK expression [10].
• We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk) [11].

Biological context of SYK

• Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified [12].
• The cytoplasmic spleen tyrosine kinase (SYK) is a key regulator of signal transduction events, apoptosis and orderly cell cycle progression in B-lineage lymphoid cells [2].
• Multivariate analyses indicated that factors affecting overall survival were tumor-node-metastasis stage, Child-Pugh classification, SYK methylation, or Syk protein status [13].
• SYK and MUSK were newly localized to the chicken Z chromosome in this study [14].
• Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation [15].

Anatomical context of SYK

• Since lethally irradiated mice reconstituted with SYK-deficient fetal liver-derived lymphohematopoietic progenitor cells show a block in B-cell ontogeny at the pro-B to pre-B cell transition, we examined the SYK expression profiles of primary leukemic cells from children with pro-B cell ALL [2].
• Closely related molecules with overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker protein, are expressed in activated NK cells and are all recruited to the center of the cytolytic synapse [16].
• Spleen tyrosine kinase (Syk) is a candidate tumor (metastasis) suppressor that is highly expressed in mammary epithelial cells [17].
• SYK, a candidate tumor suppressor, has been found not expressed in a subset of breast cancer cell lines, but the mechanism by which SYK is silenced is unclear [18].

Associations of SYK with chemical compounds

• A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase [19].
• Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a reactivation of SYK expression in SYK-negative cells, as detected by reverse transcription-PCR [18].
• NHERF tumorigenic mutations decreased or abolished its interaction with SYK or MERLIN, suggesting a pathway link among these three molecules that may play a critical role in mammary neoplastic progression [20].
• This decreased invasiveness by AZA treatment was diminished by piceatannol, a SYK inhibitor, suggesting that SYK play a significant role in AZA-inducible invasion suppression [10].
• In all five translocation-positive cases, the breakpoints were identical fusing the N-terminal pleckstrin homology domain and proline-rich region of ITK to the tyrosine kinase domain of SYK [21].

Other interactions of SYK

• The importance of DNA hypermethylation in the conversion of TCC from a low to a high malignant potential was strongly supported by the finding that, unlike superficial low-grade TCC, advanced muscle invasive TCC showed a concurrent promoter methylation of the 14-3-3 sigma, SYK and CAGE-1 genes [4].
• A spleen tyrosine kinase, Syk, in porcine B cells and a 72-kDa protein-tyrosine kinase, PTK72, in murine B cells associate with the B cell antigen receptor [22].
• The screening yielded NHERF (Na+/H+ exchanger regulatory factor, also known as NHERF1 or EBP-50) that binds to the interdomain B of SYK [20].
• Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma [23].
• In this study, we examined the 5' CpG island methylation status of the SYK gene in breast cancer cell lines and primary breast cancer tissues [18].

Analytical, diagnostic and therapeutic context of SYK

• The patients with methylated SYK in neoplastic tissues had a significantly lower overall survival rate after hepatectomy than those with unmethylated SYK [13].
• Gene-targeting studies have identified the cell types that require SYK for development and function, and the receptors that use SYK as well as their downstream signalling effectors [6].
• Using methylation-specific PCR, we demonstrated that SYK is hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the matched neighboring normal breast tissues exhibited unmethylated DNA status [18].
• Fc receptor gamma-chain and spleen tyrosine kinase (Syk) were immunoprecipitated from the lysate of platelets stimulated by vWF plus ristocetin and then analyzed by antiphosphotyrosine immunoblotting [24].

References