Ask about this productRelated genes to: TYRO3 antibody
- Gene:
- TYRO3 NIH gene
- Name:
- TYRO3 protein tyrosine kinase
- Previous symbol:
- RSE
- Synonyms:
- Dtk, Brt, Tif, Sky, Etk-2, Rek
- Chromosome:
- 15q15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-10-02
- Date modifiied:
- 2016-10-05
Related products to: TYRO3 antibody
Related articles to: TYRO3 antibody
- Patients with advanced neuroendocrine tumors (NETs) experience poor outcomes despite the use of available therapies, including molecularly targeted agents. Zanzalintinib is a novel, small-molecule inhibitor of multiple kinases, including the TAM kinases (TYRO3, AXL, MER), MET, and vascular endothelial growth factor receptors, which play important roles in oncogenic processes. Zanzalintinib has shown encouraging antitumor activity and a consistent safety profile across multiple solid tumor types in clinical trials. STELLAR-311 is a global, randomized, open-label, phase II/III trial evaluating the efficacy and safety of zanzalintinib versus everolimus in patients with advanced NETs. Adults aged ≥18 years with locally advanced/unresectable or metastatic, well-differentiated grade 1-3 NETs of pancreatic (pNET) or extra-pancreatic (epNET; gastrointestinal tract, lung, thymus, or other) origin will be enrolled. Patients with pNETs or nonfunctional epNETs can be untreated or have received up to one prior line of therapy (excluding somatostatin analogs); patients with functional epNETs must have received one prior line of therapy. The primary endpoint is progression-free survival (PFS), by blinded independent central review (BICR). Secondary endpoints include overall survival; investigator-assessed PFS; BICR- and investigator-assessed objective response rate, duration of response, and disease control rate; safety; and quality of life.Clinical trial registration www.clinicaltrials.gov identifier is NCT06943755. - Source: PubMed
Publication date: 2026/09/28
Chan Jennifer AStrosberg Jonathan RYoo ChanghoonSingh SimronHuang HuangGoel ManikaScheffold ChristianCapdevila Jaume - Although therapies targeting BTK of BCR-signal are changing the landscape of CLL management, these agents are not curative and resistance can develop. Thus, we searched for other druggable target(s) regulating leukemic B-cell survival for developing alternative therapies. We detected MERTK, a member of the TAM (Tyro3, AXL, MERTK) family receptor tyrosine kinases (RTKs), is aberrantly expressed and constitutively active in CLL cells from ~65% CLL patients (n = 100). Ligation of Gas6, a common ligand for TAM-RTKs, preferentially activated MERTK resulting in activation of NF-κB/AKT/Erk1/2 and BTK in CLL cells. Partial depletion of MERTK in CLL cells reduced P-Erk1/2, P-NF-κB, P-AKT, and P-BTK levels, suggesting that MERTK may crosstalk with BCR-signal. Indeed, MERTK activated BTK by forming a signalosome with CD79a/LYN in CLL cells. Interestingly, stimulation of BCR-signals in CLL cells activated MERTK via CD79a, suggesting that MERTK/BCR-signals are functionally connected. Importantly, targeting MERTK using a high-affinity, pharmacologic inhibitor UNC-2025 induced apoptosis in CLL cells and reduced leukemic burden in vivo. More significantly, ibrutinib-resistant CLL cells expressed high-levels of MERTK and that, UNC-2025 synergistically induced apoptosis when combined with venetoclax. Thus, high MERTK-levels in CLL cells may be associated with ibrutinib-resistance underscoring the potential use of UNC-2025/venetoclax combination in treating relapsed/refractory patients. - Source: PubMed
Publication date: 2026/09/23
Mendez Mariana TSanyal TapojyotiMamidi Murali KFernandes Stacey MVesely Sara KMraz MarekBrown Jennifer RHolter-Chakrabarty JenniferGhosh Asish K - TYRO3, AXL, and MERTK, the TAM receptor tyrosine kinases (RTKs), play roles in phagocytosis and negative regulation of immune responses, contributing to homeostasis in many adult tissues. Aberrant TAM signaling leads to diseases including autoimmune disorders, viral infection, inflammation and cancer. Development of successful drugs targeting TAM receptors is hindered by incomplete knowledge of the receptor activation mechanism. Receptor dimerization is assumed to play a role, as seen for most RTKs. However, full biological responses require the TAM ligands to engage phosphatidylserine in an opposing cell or virus membrane, suggesting a more complex mechanism, possibly involving higher-order receptor oligomerization or clustering. Here, we present an X ray crystal structure of the ectodomain of MERTK, which adopts a highly curved conformation with key interdomain boundaries stabilized by N-linked glycan moieties. We show that this MERTK extracellular region (ECR) forms a similar conformation in solution using small-angle X ray scattering (SAXS), which also suggests a flexible ECR. We compare these crystallographic and solution data for MERTK with SAXS and AlphaFold structural predictions for the other two TAM receptors. SAXS data confirm that each TAM ECR has a distinct curvature, with TYRO3 the most bent and AXL relatively straight. This leads us to speculate that these different ectodomain conformations guide receptor-specific functions. The MERTK X-ray crystal structure also suggests a head-to-tail intermolecular interaction between the Ig2 domain of one MERTK and the FNIIIb domain of a second that has intriguing parallels with interactions that have been proposed to regulate Eph receptor clustering. - Source: PubMed
Publication date: 2026/09/22
Starbird Chrystal AZuo YuhongWalker KahlilStayrook Steven EFerguson Kathryn M - Radiotherapy is a major treatment for meningioma, but radioresistance remains a key obstacle to durable disease control. Here, we show that escape from therapy-induced senescence (TIS) is a hallmark of radioresistant meningioma cells and identify a novel glycolysis-H3K27 lactylation-PROS1-TYRO3-CARF axis underlying this phenotype. Using photon-derived radioresistant meningioma models established from two independent meningioma cell lines, combined with multi-omics, CUT&Tag, dual‑luciferase reporter assays, immunoprecipitation-mass spectrometry, and in vivo xenograft analyses, we found that radioresistant cells display enhanced glycolysis, lactate accumulation, and increased H3K27 lactylation. H3K27la promotes PROS1 transcription, leading to PROS1 secretion and TYRO3 activation. Activated TYRO3 in turn promotes phosphorylation of CARF at tyrosine 8 and triggers its proteasomal degradation, relieving CDKN2A/p53-associated senescence, and permitting cell cycle re-entry. Disruption of PROS1 signaling or inhibition of CARF phosphorylation restores senescence-associated phenotypes and enhances radiosensitivity in vivo. Together, these findings establish a metabolic-epigenetic-signaling mechanism that couples glycolytic reprogramming to TIS escape in meningioma and highlight the PROS1-TYRO3-CARF axis as a potential radiosensitizing target. - Source: PubMed
Publication date: 2026/09/16
Wang ZhuohangZhang QixiangLiao KemanLiu XiaoyuZhang HongchiChen YunshengMa YuxiaoLiu YikuiXu AoqianSun YuhaoChen JiayiBian LiuguanWang Baofeng - Brain aging and sarcopenia represent multisystem manifestations of aging. Although emerging research supports the brain-muscle axis, the causal evidence and mechanisms remain unclear. - Source: PubMed
Publication date: 2026/09/16
Ye FanghangLi NaHao LiyuanYu FeiPeng QingDeng JialiHu Xiaoyu