Disease relevance of YES1

• In these studies, c-yes-/- mice exhibit decreased transcytosis of pIgA from the blood to the bile, while c-src-/- mice exhibit deficits in osteoclasts function and bone resorption [1].
• In melanoma cells in which an elevated level of c-Yes is observed, a protein of 39 kD is heavily phosphorylated on tyrosine [2].
• In MDA-MB-231 human breast cancer cells, overexpression of the small heat shock protein 27 (hsp27) results in a downregulation of c-Yes levels, concomitant with increased in vitro invasiveness and in vivo metastatic behavior [3].
• The Src family kinase c-Yes is required for maturation of West Nile virus particles [4].
• Overexpression of focal adhesion kinase (p125FAK) in human colorectal carcinoma liver metastases: independence from c-src or c-yes activation [5].

High impact information on YES1

• Here we investigate the solution structure of the WW domain of human YAP65 (for Yes kinase-associated protein) in complex with proline-rich peptides containing the core motif PPxY [6].
• Location of the c-yes gene on the human chromosome and its expression in various tissues [7].
• The transcriptional coactivator Yes-associated protein (YAP) drives p73 gene-target specificity in response to DNA Damage [8].
• Tacrolimus for active ulcerative colitis? Yes! (Even though cochrane says "no") [9].
• Src family of tyrosine kinases: a role of c-yes in colon carcinogenesis [10]?

Chemical compound and disease context of YES1

• The c-Yes 3'-UTR contains adenine/uridine-rich elements that bind AUF1 and HuR involved in mRNA decay in breast cancer cells [3].
• Is there still a role for intravenous heparin in acute stroke? Yes [11].
• Alcohol and cardiovascular disease--more than one paradox to consider. Alcohol and hypertension: does it matter? Yes [12].
• D-penicillamine in systemic sclerosis? Yes [13]!

Biological context of YES1

• The fact that W1L2 has high level (>10-fold) resistance to TS inhibitor in the absence of high YES1 expression leads to a conclusion that YES1 has no direct role in this drug resistance process [14].
• The YES1 proto-oncogene was mapped previously to human chromosome band 18q21.3 by using isotopic in situ hybridization [15].
• Chromosomal reassignment: YACs containing both YES1 and thymidylate synthase map to the short arm of chromosome 18 [15].
• Subapical EBP50 protein complexes, containing the nonreceptor tyrosine kinase c-Yes, may regulate apical signal transduction pathways leading to changes in ion transport, cytoskeletal organization, or gene expression in epithelial cells [16].
• We conclude that GC infection leads to rapid tyrosine phosphorylation of the CD46 Cyt2 tail and that the Src kinase c-Yes is involved in this reaction [17].

Anatomical context of YES1

• YES1 mRNA and protein were overexpressed in four drug-resistant tumor cell lines but were not overexpressed in the lymphoblast cell line W1L2(TDX), although the YES1 gene was highly amplified in these cells [14].
• In cultured human epidermal keratinocytes, induction of differentiation by Ca2+ and ionophore treatment was found to result in rapid elevation of c-Src tyrosine kinase activity and inactivation of the c-Yes tyrosine kinase [18].
• Three c-yes cDNA clones were obtained from poly(A)+ RNA of human embryo fibroblasts [19].
• The protein level of c-Yes in these melanoma cell lines is correspondingly higher than that in melanocytes [2].
• These data suggest that derangement of expression of the c-Yes tyrosine kinase may have a role in the malignant progression of the human melanocyte [2].

Associations of YES1 with chemical compounds

• Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets [20].
• Finally, c-Yes immunoprecipitated from epithelial cells is able to phosphorylate the wild-type Cyt2 tail but not the mutant derivative in which tyrosine 354 has been substituted with alanine [17].
• A constitutively active form of c-Yes was observed to decrease the binding affinity between YAP and p53BP-2 using chloramphenicol acetyltransferase/enzyme-linked immunosorbent assay, whereas the overexpression of c-Yes did not modify this interaction [21].
• Mutation of the tyrosine autophosphorylation site of Yes to a phenylalanine resulted in a mutant Yes enzyme that can be fully inactivated by a sub-stoichiometric amount of Csk in a time-dependent manner [22].
• These results suggest that cAMP activates while Ca(2+) inhibits human sperm c-yes kinase activity [23].

Physical interactions of YES1

• Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells [24].

Co-localisations of YES1

• Moreover, we demonstrate in this study that occludin was colocalized with the nonreceptor tyrosine kinase c-Yes at cell junction areas and formed an immunoprecipitable complex with c-Yes in vivo [24].

Other interactions of YES1

• In addition, we show that the nonreceptor tyrosine kinase c-Yes is contained within EBP50 protein complexes by association with YAP65 [16].
• We have found that two different regions of QM protein were associated with the SH3 domain of c-Yes [25].
• Taken together, these results suggest that YES1, TYMS, HEC and TGIF are likely to be candidate targets for 18p11.3 amplification and be associated with esophageal tumorigenesis [26].
• Only four known genes, YES1, TYMS, HEC and TGIF showed amplification and consequent over-expression [26].
• We report here the map location of a Xiphophorus yes gene, YES1, in LG VI, closest to the EGFR gene and the assignment of a fyn gene homologue to newly designated LG XV, linked to the gene for cytosolic alpha-galactosidase [27].

Analytical, diagnostic and therapeutic context of YES1

• Immunofluorescence studies showed that the QM proteins and c-Yes are able to interact in various tumor cell lines in vivo [25].
• Sequence analysis of the clones showed that they contained inserts corresponding to nearly full-length human c-yes mRNA, which could encode a polypeptide of 543 amino acids with a relative molecular weight (Mr) of 60,801 [19].
• Expression of the c-yes proto-oncogene in normal mammalian tissues was studied by immunohistochemistry and by immunoprecipitation assays using affinity purified anti-yes IgG [28].
• In contrast electroporation of antibodies against c-Yes or c-Fyn had no effect [29].
• 1. Western blot analysis with specific antibodies against Src family members showed expression of Src, Fyn, and Lyn, lower levels of Yes and Hck, and the absence of Lck tyrosine kinase [30].

References