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Rat and mouse FGF-9 show a very high homology to human FGF-9. The transcripts for FGF-9 have been found in brain and in kidney tissue. Fibroblast Growth Factor-9 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF9 was isolated as a secreted factor that exhibits a growth-stimulating effect on cultured glial cells. In nervous system, this protein is produced mainly by neurons and may be important for glial cell development. Expression of the mouse homolog of this gene was found to be dependent on Sonic hedgehog (Shh) signaling. Mice lacking the homolog gene displayed a male-to-female sex reversal phenotype, which suggested a role in testicular embryogenesis Fibroblast Growth Factor 9 may have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors.

Receptor-associated Protein (aka RAP) averts the GCM-mediated enhancement of axon growth- ApoE-containing lipoproteins which are known to bind to receptors of the LDLr superfamily. In the presence of RAP, GCM doesn’t increase the axon extension rate in relation to base medium. Furthermore, the addition of RAP to the base medium doesn’t change the rate of axon extension. This implies that the growth stimulatory effect of apoE-containing lipoproteins secreted by glial cells is mediated by the LDLr family receptors. RAP annuls the growth stimulatory effect of GCM.

SLAM family member 6 (SLAMF6) is a member of the SLAM family of immune cell receptors. SLAMF6 is a unique receptor on T cells which, when triggered potentiates T cell expansion in a CD28-independent manner. SLAMF6 has a high expression on NK-, T-, and B cells. SLAMF6 exhibits homotypic interactions and can connect with adaptor molecules such as SAP to alter immune cell function.

The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding.

CD23 is a 45kDa glycoprotein, which is present on a subpopulation of freshly isolated peripheral blood and tonsil B cells and strongly expressed on EBV-transformed B lymphoblasts. The CD23 molecule is identical to the low affinity IgE receptor found on B cells. Expression of CD23 has been detected in neoplastic cells from cases of B cell chronic lymphocyctic leukaemia and some cases of centroblastic/centrocytic lymphoma.

IL2-Ra is one of the three constituent subunits of the IL2 receptor. IL-2Ra is released into the serum after increased cellular expression such as increased activation of B and T cells. Clinical manifestations of IL2-Ra elevation include autoimmune conditions and some leukemias and lymphomas.

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8) is a receptor for TNFSF8/CD30L. TNFRSF8 has a role in the regulation of cellular growth and transformation of activated lymphoblasts. In addition, the TNFRSF8 protein regulates gene expression via activation of NF-kappa-B. TNFRSF8 being a regulator of apoptosis, induces cell death or proliferation, depending on the cell type.

The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of fas-mediated apoptosis using similar mechanisms.

RAMP belongs to the type I transmembrane family of proteins called RAMP (receptor/calcitonin activity modifying proteins) which include an extracellular N terminus and a cytoplasmic C terminus. RAMPs are essential for CRLR transport to the plasma membrane. CRLR (calcitonin-receptor-like receptor) has seven transmembrane domains. Depending on which members of the RAMP family are expressed CRLR receptor functions as either an adrenomedullin receptor or a calcitonin-gene-related peptide (CGRP) receptor. In the presence of RAMP1, CRLR functions as a CGRP receptor. The RAMP1 protein takes part in the terminal glycosylation, maturation, and presentation of the CGRP receptor to the cell surface.

IL-1Ra is the natural antagonist of the pro-inflammatory cytokines Interleukin-1? and Interleukin-1?. IL-1Ra is produced by a variety of cells including monocytes, macrophages, neutrophils and fibroblasts in response to the binding of various pro-inflammatory cytokines.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. By injecting soluble RANKL, novel osteopenia model mice were established in only 50 hours. Degree of bone loss can be controlled by changing doses of sRANKL. RANKL can be used in establishing osteopenia model for in vivo screening of drugs for osteoporosis, determination of effect and mechanism, evaluation of bone anabolic drugs.

Coagulation factor VII is a vitamin K-dependent factor which is essential for hemostasis. It circulates in the blood as a zymogen which is later converted to an active form by factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of factor VII, a heavy chain with a catalytic domain and a light chain with 2 EGF-like domains are generated, and the two chains are held together by a disulfide bond. The presence of factor III and calcium ions further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Alternative splicing of factor VII results in 2 transcripts. Defects in coagulation factor VII can cause coagulopathy. Coagulation factor VII initiates the extrinsic pathway of blood coagulation. Minor proteolysis converts factor VII to factor VIIa by factors Xa, XIIa, IXa, or thrombin. Factor VIIa also converts factor IX to factor IXa in the presence of tissue factor and calcium.

T-cell surface glycoprotein CD3 zeta chain (CD247) is a member of the CD3Z/FCER1G family. CD247 is T-cell receptor zeta, which along with T-cell receptor alpha/beta and gamma/delta heterodimers, and also with CD3-gamma, -delta and -epsilon, creates the T-cell receptor-CD3 complex. The zeta chain has a central role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the CD247 antigen causes impaired immune response.

Interleukin 11 Receptor Subunit Alpha (IL11RA) which belongs to the hematopoietic cytokine receptor family is a receptor for interleukin-11. Interleukin 11 is a stromal cell-derived cytokine which is a member of a family of pleiotropic and redundant cytokines that employ the gp130 transducing subunit in their high affinity receptors. This specific receptor is quite similar to ciliary neurotrophic factor, since both contain an extracellular region with a two-domain structure composed of an immunoglobulin-like domain and a cytokine receptor-like domain. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 are able to utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex is involved in the control of proliferation and/or differentiation of skeletogenic progenitor or additional mesenchymal cells.

TLR2 belongs to the Toll-like receptor (TLR) family that plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) which are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. TLR2 is expressed most abundantly in peripheral blood leukocytes, and mediates host response to Gram-positive bacteria and yeast via stimulation of NF-kappaB.

FADD is an adaptor protein that cooperates with a variety of cell surface receptors and mediates cell apoptotic signals. Using its C-terminal death domain, FADD is recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and consequently it take parts in the death signaling initiated by these receptors. FADD interaction with the receptors reviels the N-terminal effector domain of, which allows it to recruit caspase-8, and thus initiate the cysteine protease cascade. Knockout studies in mice furthermore propose the significance of FADD in premature T cell development. FADD plays a role in survival/proliferation and cell cycle development. FADD also takes part in cellular sublocalization, protein phosphorylation, and inhibitory molecules.

Cytotoxicity Triggering Receptor 3 also known as NCR3 is a natural cytotoxicity receptor (NCR) which assists NK cells in the lysis of tumor cells. Moreover, NCR3 interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of NCR3 has been related with mild malaria suceptibility. Three transcript variants encoding various isoforms have been found for this gene.

IL17 is a proinflammatory cytokine produced by activated T cells. IL-17 regulates the activities of NF-kappaB and mitogen-activated protein kinases. Interleukin-17 can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis.

CD40 belongs to the TNF-receptor super family. CD40 has been found to be vital in mediating a wide range of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is accounted to coordinately regulate the expression of CD40 and its ligand, which is significant for homotypic cell interactions. Adaptor protein TNFR2 interacts with CD40 and functions as a mediator of the signal transduction. The interaction of CD40 and its ligand is found to be essential for amyloid-beta-induced microglial activation, and therefore is considered to be an early event in Alzheimer disease pathogenesis.

CXADR Like Membrane Protein or CLMP, part of the CTX family within the immunoglobulin superfamily, is a type 1 transmembrane peptide. CLMP is expressed in the placenta and small intensine, skeletal muscle, colon, lungs and heart. CLMP is located in junction complexes across endothelial and epithelial cells and can take part in cell adhesion. The protein has influence on development of obesity via adipocyte differentiation.

Prolactin is a pituitary hormone involved in the stimulation of milk production, salt and water regulation, growth, development and reproduction. The initial step in its action is the binding to a specific membrane receptor (prolactin receptor) which belongs to the superfamily of class 1 cytokine receptors. The function of the prolactin receptor is mediated, at least in part, by two families of signaling molecules: Janus kinases and signal transducers and activators of transcription. Prolactin (PRL) is a hormone involved in a variety of important functions including ion transport and osmoregulation, stimulation of milk, protein synthesis as well as the regulation of numerous reproductive functions. PRL exerts its influence on different cell types through a signal transduction pathway which begins with the binding of the hormone to a transmembrane PRL receptor. Immunoreactive PRL receptor, a member of the cytokine receptor family, varies in size (short and long forms) with tissue source and species, from ~40 kDa to 100 kDa. The PRL receptor consists of at least three separate domains: an extracellular region with 5 cysteines which contains the prolactin binding site, a single transmembrane domain and a cytoplasmic region, the length of which appears to influence ligand binding and regulate cellular function.

Osteoclasts are multinucleated cells that resorb bone and are essential for bone homeostasis. OSCAR plays crucial roles in the regulation of the innate and adaptive immune responses.Unlike the other LRC members, OSCAR expression is found specifically in preosteoclasts or mature osteoclasts. OSCAR is an important bone-specific regulator of osteoclast differentiation. Multiple alternative splicing transcript variants encodes different isoforms have been found for this gene.

Herpesvirus entry mediator or HVEM or tumour necrosis factor receptor superfamily member 14 or TNFRSF14, is part of the TNF receptors family that is a receptor located on the cell surface. The cytoplasmic area of this receptor can bind all sorts of TNF receptor associated factor (TRAF) protein. Those proteins can mediate pathways activating an immune response. The MITF is regulating TNFRSF14 gene expression.