Also, genes that code
for receptor tyrosine kinases, a family of receptors on the surface of cells, may rearrange to form multiple distinct gene fusion partners, as evidenced in an article by Kulkarni, et al, on a translational study involving a patient who developed a BRAF fusion following treatment with a BRAF inhibitor1.
Not exact matches
The target
for ibrutinib, an enzyme called Bruton's
tyrosine kinase (BTK), is a key component of B - cell
receptor signaling.
Epidermal growth factor
receptor (EGFR)
tyrosine kinase inhibitors (TKIs) are the preferred treatment option
for patients with advanced non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene.
D'Oro, U., Vacchio, M.S., Weissman, A.M. & Ashwell, J.D. Activation of the Lck
tyrosine kinase targets cell surface T cell antigen
receptors for lysosomal degradation.
(h) Human phospho -
receptor tyrosine kinase array
for EphA2, EphB2 and EphB4 ephrin
receptors from control BP (shCtr) and BP silenced
for Tie2 (siTie2 I and siTie2 II).
Further, we identified a role
for ABL
kinases in promoting the expression of multiple pro — bone metastasis genes such as AXL (which encodes a
receptor tyrosine kinase), IL6 (which encodes interleukin - 6), MMP1 (which encodes matrix metalloproteinase 1), and TNC (which encodes tenascin - C) through TAZ - and signal transducer and activator of transcription 5 (STAT5)-- mediated signaling.
The initial model
for STAT signaling involves a specific cytokine binding to its cognate
receptor and promoting the transphosphorylation of
receptor associated
tyrosine kinases from the Janus - activated
kinase family (JAK).
In 2005, the identification of an activating mutation in JAK2 (the V617F mutation) as a STAT5 - activating and disease - causing genetic alteration in a significant proportion of patients with myeloproliferative neoplasms (MPNs) has emphasized the oncogenic role of the JAK
tyrosine kinases in hematologic malignancies.2 — 5 JAK2 is a member of the Janus
tyrosine kinase family comprising three other mammalian non-receptor
tyrosine kinases (JAK1, JAK3 and TYK2) that associate with cytokine
receptors lacking intrinsic
kinase activity to mediate cytokine - induced signal transduction and activation of STAT transcription factors.6 All JAKs share a similar protein structure and contain a
tyrosine kinase domain at the C - terminus flanked by a catalytically inactive pseudokinase domain with
kinase - regulatory activity, by an atypical SH2 domain and by a FERM domain that mediates association to the membrane - proximal region of the cytokine
receptors.7, 8 Soon after the discovery of JAK2 V617F, we and others described that activating JAK1 mutations are relatively common in adult patients with T - cell acute lymphoblastic leukemia (ALL) and participate in ALL development allowing
for constitutive activation of STAT5.9 — 11 Several STAT5 - activating JAK1 mutations were also reported in AML and breast cancer patients.10
In addition, at least some Eph
receptors can also signal through non-canonical mechanisms that are independent of ligand binding and
kinase activity,
for example through interplay with other
receptor tyrosine kinase families and with serine / threonine
kinases.
For example, our past work showed that two conserved
tyrosine phosphorylation sites in the juxtamembrane segment of the Eph
receptors not only mediate association with binding partners but also regulate
receptor kinase activity.
Today, it is estimated that about a third of pharmaceutical research and development effort goes into targeting
tyrosine kinase receptors and their signaling pathways
for cancer therapies.
METHODS: We treated 3T3 - L1 adipocytes with 2.5 mmol / l R (+) alpha - lipoic acid
for 2 to 60 min, followed by assays of: 2 - deoxyglucose uptake; glucose transporter 1 and 4 (GLUT1 and GLUT4) subcellular localization;
tyrosine phosphorylation of the insulin
receptor or of the insulin
receptor substrate - 1 in cell lysates; association of phosphatidylinositol 3 -
kinase activity with immunoprecipitates of proteins containing phosphotyrosine or of insulin
receptor substrate - 1 using a in vitro
kinase assay; association of the p85 subunit of phosphatidylinositol 3 -
kinase with phosphotyrosine proteins or with insulin
receptor substrate - 1; and in vitro activity of immunoprecipitated Akt1.
Multi-center, placebo - controlled, double - blind, randomized study of oral toceranib phosphate (SU11654), a
receptor tyrosine kinase inhibitor,
for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision.
«In the near future, we'll likely see more medications specifically targeting
receptors on cells involved in allergic reactions, such as
tyrosine kinase inhibitors (mast cells),
for dermatologic use.»