Tyrosine-protein kinase Mer (MERTK) is a single-pass type I membrane protein which belongs to the MER/AXL/TYRO3 receptor kinase family. MERTK include two fibronectin type-III domains; two Ig-like C2-type domains; and one tyrosine kinase domain. It can’t be expressed in normal B- and T-lymphocytes; but it is usually expressed in numerous neoplastic B- and T-cell lines. MERTK could regulate many physiological processes; such as cell survival; migration; differentiation. It was demonstrated that the MERTK plays critical role in the engulfment and efficient clearance of apoptotic cells; platelet aggregation; and cytoskeleton reorganization. Not only these; it also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1; which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. In addition; MERTK could regulate rod outer segments fragments phagocytosis in the retinal pigment epithelium (RPE); deficiency in MERTK are the cause of retinitis pigmentosa.
LDLR chaperone MESD, also known as Mesoderm development protein, Mesoderm development candidate 2, Renal carcinoma antigen NY-REN-61 and MESDC2, is a member of the MESD family. MESDC2 is a chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). The LDLR maturation activity resides in the N- and C-terminal unstructured regions. MESDC2 acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway. MESDC2 is essential for specification of embryonic polarity and mesoderm induction.
Megakaryocyte potentiating factor belongs to the mesothelin family. This family is comprised by several mammalian pre-pro-megakaryocyte potentiating factor precursor (MPF) or mesothelin proteins. Mesothelin is a glycosylphosphatidylinositol-linked glycoprotein highly expressed in mesothelial cells; mesotheliomas; and ovarian cancer; but the biological function of the protein is not known. Megakaryocyte potentiating factor is highly expressed in mesotheliomas; ovarian cancers; and some squamous cell carcinomas (at protein level). It interacts with MUC16 and potentiates megakaryocyte colony formation in vitro. Megakaryocyte potentiating factor is secreted by several mesothelioma cell lines and is frequently elevated in the blood of patients with mesothelioma. Measurement of this protein may be useful in following the response of mesothelioma to treatment.
Mesothelin is a cell surface glycoprotein whose expression is limited to mesothelial cells of the serosa (pleura; pericardium; and peritoneum) and epithelial cells of the trachea; tonsils; fallopian tube; and kidneys. Mesothelin plays an important role in cell survival; proliferation; migration; invasion; tumor progression; and resistance to chemotherapy. The overexpression of mesothelin can activate NF-κB and signal transducer and activator of transcription 3 (Stat3); inhibit apoptotic signaling and TNF-α-induced apoptosis; and accelerate the G1–S transition. Mesothelin is also found overexpressed in various cancers; including malignant mesothelioma; pancreatic or ovarian carcinoma; sarcomas and in some gastrointestinal or pulmonary carcinomas. As a result of its limited expression in normal tissues; mesothelin has been reported as an ideal tumor-associated marker for the development of targeted therapy.
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