The cytokine thymic stromal lymphopoietin receptor (TSLPR) is consisting of a common γ receptor–like chain (TSLPR-γ) and a common interleukin 7 (IL-7) Rα chain that belongs to the type 1 cytokine receptor family. Transfection of TSLPR cDNA result in only low affinity binding, while cotransfection of the IL-7Rα chain cDNA shows high affinity binding. TSLP and TSLPR play a critical role in the initiation of allergic diseases in mice. The TSLP R cDNA encodes a transmembrane receptor containing 370 amino acids (aa) with two potential N-linked glycosylation sites and a cytoplasmic domain of 104 aa including a single tyrosine residue. TSLPR can mediate signaling of the signal transducer and activator of transcription 5 (Stat5) by TSLP. TSLP R is broadly expressed in the immune and hematopoietic cells, particularly in hematopoietic progenitors and myeloid cells.
TWSG1 belongs to the twisted gastrulation protein family. TWSG1 from different species are functionally equivalent. In contrast to Drosophila where TWSG1 expression is limited to early embryos, expression of TWSG1 is found throughout mouse and human development. Mutations in the TWSG1 gene cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates. This is thought to involve gradients of the signaling molecule decapentaplegic. TWSG1 may function as a bone morphogenetic protein signalling agonist or antagonize these activities. It can dislodge latent bone morphogenetic proteins and thus provides a permissive signal that allows high BMP signaling in the embryo. TWSG1 is a cofactor in the antagonism of chordin to BMP signaling. It also binds both the vertebrate Decapentaplegic ortholog BMP4 and chordin and forms ternary complexes. Meanwhile, TWSG1 increases binding of chordin to BMP4, potentiates the ability of chordin to induce secondary axes in Xenopus embryos, and enhances chordin cleavage by vertebrate proteases related to tolloid at a site poorly used in the absence of TWSG1. The presence of TWSG1 enhances the secondary axis-inducing activity of 2 products of chordin cleavage.
Dtk, also called Tyro3, belongs to the TAM receptor family of receptor protein tyrosine kinases (RPTKs) composed of three receptors Tyro3, Axl, and Mer. These receptors share a characteristic molecular structure of two immunoglobulin-like and two fibronectin type III repeats and have been best characterized for their roles in immune regulation, fertility, thrombosis and phagocytosis. Gas6 and protein S have been identified as ligands for these receptors. Gas6 binding induces tyrosine phosphorylation and downstream signaling pathways that can lead to cell proliferation, migration, or the prevention of apoptosis. Tyro3 and Axl play important regulatory roles in a variety of tissues, including the central nervous, reproductive, immune, and vascular systems. Tyro3 is widely expressed during embryonic development and preferentially expressed during neurogenesis in the central nervous system.
Axl, also known as Ufo and Ark, is a widely expressed 140 kDa glycoprotein in the TAM receptor tyrosine kinase family. Axl binds the vitamin K-dependent protein Gas6 which triggers tyrosine autophosphorylation of the Axl cytoplasmic domain. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is highly expressed in solid cancers and promotes in vivo tumorigenesis and tumor cell invasiveness. It also functions as a cellular entry receptor for Gas6-opsonized lentiviruses. Axl contributes to cell survival, migration, invasion, metastasis and chemosensitivity justify further investigation of Axl as novel therapeutic targets in cancer. The receptor tyrosine kinase AXL is thought to play a role in metastasis. The soluble AXL receptor as a therapeutic candidate agent for treatment of metastatic ovarian cancer. GAS6/AXL targeting as an effective strategy for inhibition of metastatic tumor progression in vivo.
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds (PubMed:2517217). Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine.
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