YES1 Antibody
Description
Introduction to YES1 Antibody
YES1 antibodies are proteins designed to bind specifically to YES1, a non-receptor tyrosine kinase involved in cell proliferation, survival, adhesion, and drug resistance in cancers . These antibodies enable researchers to investigate YES1 expression, localization, and signaling mechanisms in both normal and malignant tissues.
Key Antibody Characteristics
Below are technical specifications of commercially available YES1 antibodies:
WB = Western blot; IHC = Immunohistochemistry; ICC/IF = Immunocytochemistry/Immunofluorescence; IP = Immunoprecipitation.
Diagnostic and Mechanistic Studies
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Drug Resistance: YES1 amplification is linked to resistance against HER2-targeted therapies (e.g., trastuzumab-emtansine) and EGFR inhibitors (e.g., erlotinib) . Antibodies like ab109744 have been used to validate YES1 overexpression in resistant cell lines .
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Oncogenic Signaling: YES1 activates pathways such as EGFR, PI3K/AKT, and MAPK, contributing to tumor growth. Antibodies enable detection of YES1 phosphorylation (e.g., Tyr426) to study signaling dynamics .
Therapeutic Development
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Target Validation: Preclinical studies using YES1 inhibitors (e.g., CH6953755) rely on antibodies to confirm target engagement and suppression of YES1 activity in xenograft models .
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Biomarker Identification: High YES1 expression correlates with poor prognosis in lung, breast, and esophageal cancers . IHC with YES1 antibodies helps stratify patient populations .
Western Blot
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ab109744: Detects YES1 at 60 kDa in A431 (human epidermal carcinoma) and NIH 3T3 (mouse fibroblast) cell lines .
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67196-1-Ig: Validated in A549 (lung), HepG2 (liver), and HeLa (cervical) cancer cells .
Immunohistochemistry
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ab109744: Stains YES1 in formalin-fixed paraffin-embedded (FFPE) human breast and placental tissues .
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67196-1-Ig: Effective in human kidney tissue with antigen retrieval .
Clinical Relevance
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Resistance Mechanisms: YES1 amplification drives cross-resistance to HER2-targeted therapies by activating bypass signaling pathways (e.g., EGFR, MAPK) .
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Therapeutic Targeting: Combining YES1 inhibitors (e.g., dasatinib) with HER2-targeted agents reverses resistance in preclinical models .
Limitations and Considerations
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Specificity: Some antibodies may cross-react with other SFK members due to structural homology.
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Sample Handling: Optimal results require specific fixation methods (e.g., methanol for ICC/IF) .
Future Directions
Product Specs
Target Background
YES1 is a non-receptor protein tyrosine kinase that plays a crucial role in regulating various cellular processes, including cell growth, survival, apoptosis, cell-cell adhesion, cytoskeletal remodeling, and differentiation. Activation of YES1 is often triggered by receptor tyrosine kinase (RTK) stimulation, including those of EGFR, PDGFR, CSF1R, and FGFR. This stimulation leads to YES1 recruitment to the phosphorylated receptor, subsequent activation, and phosphorylation of downstream substrates. Specifically, YES1:
- Promotes epithelial tight junction assembly by phosphorylating PARD3 upon EGFR activation.
- Participates in the phosphorylation of junctional components such as CTNND1 via the stimulation of FYN and FER tyrosine kinases at cell-cell contacts.
- Phosphorylates collapsin response mediator protein 2 (DPYSL2) following CXCL12-mediated T-cell stimulation, thereby inducing T-cell migration.
- Mediates AKT-dependent cell migration within the CD95L/FASLG signaling pathway.
- Regulates G1 phase progression by phosphorylating cyclin-dependent kinase 4 (CDK4).
- Is involved in G2/M progression and cytokinesis.
Numerous studies highlight the significant involvement of YES1 in various cancers and cellular processes. Key findings include:
- YES1 mediates the regulation of miR-199a, contributing to paclitaxel resistance in prostate cancer. (PMID: 29204706)
- Acquired YES1 amplification represents a recurring and targetable mechanism of resistance to EGFR inhibition in EGFR-mutant lung cancers. (PMID: 29875142)
- miR-140-5p inhibits tumorigenesis in gastric cancer by targeting YES1. (PMID: 28818100)
- H19 acts as a competitive endogenous RNA (ceRNA) for miR-17-5p, influencing YES1 expression. (PMID: 27093644)
- YES1 plays a critical role in the migration and invasion of epithelial ovarian cancer cells. (PMID: 27289010)
- miR-210 inhibits hepatocellular carcinoma cell proliferation by targeting YES1. (PMID: 26676187)
- miR-203 induces apoptosis in KB cells by directly targeting YES1, suggesting therapeutic potential. (PMID: 25910964)
- Phosphorylated FAK Y861 and increased YES1 expression may serve as predictive markers for prostate cancer metastasis. (PMID: 25868388)
- miR-17-5p may regulate YES1 expression in human ovarian cancer. (PMID: 25561420)
- Increased YES/SFK activation may predict tumor resistance to IGF-1R inhibition. (PMID: 25925378)
- YES1 and YAP transcript levels are elevated in liver metastases of colon cancer patients following 5FU-based neoadjuvant chemotherapy. (PMID: 24323901)
- YES kinase acts as a proximal glucose-specific signal in the Cdc42 signaling cascade. (PMID: 24610809)
- CRKL/YES pathways are crucial for rhabdomyosarcoma cell growth and survival, suggesting a potential therapeutic role for SRC family kinase inhibition. (PMID: 23318429)
- HPV type 16 E7 expression increases Src and YES1 protein levels. (PMID: 23497302)
- YES1 and Lyn phosphorylate EGFR at Y1101, influencing EGFR nuclear translocation in cetuximab resistance. (PMID: 22430206)
- YES1 is a central mediator of malignant mesothelioma cell growth. (PMID: 22948717)
- YES1 regulates oncogenic signaling pathways crucial for colon cancer progression. (PMID: 21390316)
- YES1 activation is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3. (PMID: 21454696)
- YES1 may play diverse roles in different lung tumor subtypes. (PMID: 21190720)
- YES1 is expressed in malignant melanoma and squamous cell carcinoma. (PMID: 20796316)
- YES1 and STAT1 are direct miR-145 targets. (PMID: 20098684)
- Somatic mutations in YES1 have been identified in KRAS/BRAF wild-type tumors. (PMID: 19893451)
- IFIH1, a type 1 diabetes susceptibility gene, interacts with YES1, influencing glucose transport. (PMID: 19797678)
- cAMP activates, while Ca2+ inhibits, human sperm c-yes kinase activity. (PMID: 12080032)
- QM binds to c-yes at the SH3 domain in tumor cell lines. (PMID: 12138090)
- c-Yes modulates signals distinct from c-Src. (PMID: 12456296)
- YES1 triggers hyperosmotic activation of the epidermal growth factor receptor and CD95. (PMID: 15039424)
- c-Yes activation is crucial for maintaining embryonic stem cells in an undifferentiated state. (PMID: 15148312)
- c-Yes 3'-UTR contains AREs bound by HuR and AUF1. (PMID: 16289864)
- VEGF-induced cell migration is reduced in Yes-deficient retinal microvascular endothelial cells. (PMID: 16400523)
- c-Yes activation may play a role in hepatocyte malignant transformation. (PMID: 17007035)
- OPCML, RNASE1, YES1, and ACK1 may play key roles in gastric cancer tumorigenesis and metastasis. (PMID: 17109515)
- Nucleus-located c-Yes may be a useful marker for early-stage hepatocellular carcinoma. (PMID: 17143518)
- An SH3 domain from the Src family participates in amyloid aggregation. (PMID: 17418139)
- c-Src, c-Yes, and Lyn are differentially activated through Cdc2 activation during M phase. (PMID: 17692281)
- c-Yes induction increases colorectal carcinoma cell motility but not proliferation. (PMID: 17898870)
- YES1 recruitment to CD95 signals invasion via the glycogen synthase kinase 3-beta pathway in glioblastoma cells. (PMID: 18328427)
- SFK trafficking is specified by the palmitoylation state in the SH4 domain. (PMID: 19258394)
Q&A
How do I select an appropriate YES1 antibody for Western blotting (WB) versus immunohistochemistry (IHC)?
Methodological guidance:
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Antigen retrieval: For IHC, use TE buffer (pH 9.0) or citrate buffer (pH 6.0) for optimal epitope exposure in formalin-fixed tissues .
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Dilution ranges:
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Validation criteria: Prioritize antibodies with demonstrated reactivity in specific cell lines (e.g., A549, HEK-293) and cancer tissues (lung, colon) .
Table 1: Antibody Performance in Common Applications
What controls are essential for verifying YES1 antibody specificity?
Best practices:
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Knockout (KO) validation: Use CRISPR/Cas9-generated YES1-KO cell lysates (e.g., KYSE70 esophageal cancer cells) .
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Cross-reactivity checks: Test against SRC family kinases (e.g., FYN, LCK) due to structural homology .
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Orthogonal validation: Compare results across multiple clones (e.g., monoclonal E04/5H12 vs. polyclonal 20243-1-AP) .
How do I resolve discrepancies in YES1 molecular weight across studies?
Technical analysis:
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Post-translational modifications: Phosphorylation or ubiquitination may shift observed MW (e.g., 61 vs. 62 kDa in vs. ).
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Gel conditions: Optimize SDS-PAGE concentration (7.5–10%) to improve resolution .
Table 2: Reported YES1 Molecular Weights
What mechanistic insights can YES1 antibodies provide in cancer research?
Case study:
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YAP1 regulation: In YES1-amplified cancers (esophageal, lung), YES1 inhibition reduces YAP1 nuclear translocation and phosphorylation, impairing tumor growth .
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Therapeutic targeting: CH6953755 (YES1 inhibitor) shows efficacy in xenograft models, highlighting YES1 as a druggable target .
Table 3: YES1 Amplification in Human Cancers
How can I optimize co-immunoprecipitation (Co-IP) for YES1 interactome studies?
Protocol refinement:
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Lysis buffer: Use RIPA buffer with phosphatase/protease inhibitors to preserve phosphorylation states .
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Antibody ratio: 0.5–4.0 µg antibody per 1–3 mg lysate (Proteintech) .
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Elution validation: Confirm interactions via Western blotting for known binding partners (e.g., CD46 in Neisseria infection models) .
Why do some studies report YES1 overexpression while others observe no functional impact?
Critical analysis:
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Context-dependent roles: YES1 promotes tumor growth in YES1-amplified models but shows redundant roles in non-amplified contexts due to SRC compensation .
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Antibody specificity: False positives may arise from cross-reactivity with SRC; validate using KO controls .
