smooth muscle cell

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. ACTA2 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 47.8 kDa and the accession number is P62736.

DENR Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 38.0 kDa and the accession number is O43583.

Platelet-Derived Growth Factor Subunit B (PDGFB) belongs to the PDGF/VEGF growth factor family. Platelet-derived growth factor is a potent mitogen for cells of mesenchymal origin. PDGFB can exist either as a homodimer (PDGF-BB) or as a heterodimer with the platelet-derived growth factor alpha polypeptide (PDGF-AB), where the dimers are connected by disulfide bonds. As growth factor，it plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. It is required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. PDGFB also plays an important role in wound healing.

Leukotriene C4 synthase, also known as LTC4 synthase, Leukotriene-C(4) synthase, and LTC4S, is a multi-pass membrane protein that belongs to the MAPEG family. LTC4S is detected in the lung, platelets, and the myelogenous leukemia cell line KG-1 (at protein level). LTC4S activity is present in eosinophils, basophils, mast cells, certain phagocytic mononuclear cells, endothelial cells, vascular smooth muscle cells, and platelets. LTC4S is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. Mutagenic analysis of the conjugation function of human LTC4S has identified R51 and Y93 as critical for acid and base catalysis of LTA4 and reduced glutathione, respectively. A comparison across species for proteins that possess LTC4S activity reveals conservation of both of these residues, whereas R51 is absent in the FLAP molecules. Thus, within the glutathione S-transferase superfamily of genes, alignment of specific residues allows the separation of LTC4S family members from their most structurally similar counterparts, the FLAP molecules. Defects in LTC4S are the cause of leukotriene C4 synthase deficiency (LTC4 synthase deficiency). LTC4 synthase deficiency is a fatal neurometabolic developmental disorder. It is associated with muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly.

Thrombospondin type-1 domain-containing protein 1, also known as transmembrane molecule with thrombospondin module, THSD1 and TMTSP, is a single-pass type I membrane protein that contains one TSP type-1 domain. THSD1 is a multi-domain, multi-functional glycoprotein synthesized by many cells. Matricellular THSD1 modulates cell adhesion and proliferation. It is involved in angiogenesis, inflammation, wound healing and cancer. In vitro, nanomolar concentrations of Thrombospondin-1 are required to alter endothelial and vascular smooth muscle cell adhesion, proliferation, motility, and survival. As a major platelet protein, for a long time it was postulated to control hemostasis via platelet aggregate stabilization. THSD1 is a potent angiogenesis inhibitor, and down-regulation of THSD1 has been suggested to alter tumor growth by modulating angiogenesis in a variety of tumor types.

Death-associated protein kinase 3, also known as DAP kinase 3, ZIP-kinase, DAPK3 and ZIPK, is a nucleus and cytoplasm protein which belongs to theprotein kinase superfamily, CAMK Ser/Thr protein kinase family and DAP kinase subfamily. DAPK3 / ZIPK contains oneprotein kinase domain. It is a serine/threonine kinase which acts as a positive regulator of apoptosis. It phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. DAPK3 / ZIPK is a homodimer or forms heterodimers with ATF4. Both interactions require an intact leucine zipper domain and oligomerization is required for full enzymatic activity. It also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. DAPK3 / ZIPK regulates myosin light chain phosphatase through phosphorylation of MYPT1 thereby regulating the assembly of the actin cytoskeleton, cell migration, invasiveness of tumor cells, smooth muscle contraction and neurite outgrowth. It is involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection.

Heparin-binding EGF-like growth factor (HBEGF), a member of the EGF family of growth factors, exerts its biological activity through activation of the EGFR and other ErbB receptors. Soluble mature HBEGF is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen and chemotactic factor for fibroblasts, smooth muscle cells but not endothelial cells. HBEGF activates two EGF receptor subtypes, HER1 and HER4, and binds to cell surface HSPG. The transmembrane form of HBEGF is a juxtacrine growth and adhesion factor and is uniquely the receptor for diphtheria toxin. Both forms of HB-EGF participate in normal physiological processes and pathological processes including tumor progression and metastasis, organ hyperplasia, and atherosclerotic disease. HBEGF participates in diverse biological processes, including heart development and maintenance, skin wound healing, eyelid formation, blastocyst implantation, the progression of atherosclerosis, and tumor formation, through the activation of signaling molecules downstream of ErbB receptors and interactions with molecules associated with HBEGF. tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta markedly increased HB-EGF mRNA levels in HUVEC by 12- and 7-fold, respectively, and induction of the gene by TNF-alpha was both dose- and time-dependent.

C-Kit/SCF R is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). c-Kit contains 5 Ig-like C2-type (immunoglobulin-like) domains and 1 protein kinase domain. It belongs to the protein kinase superfamily and CSF-1/PDGF receptor subfamily. SCF R expression on mast cells enables them to infiltrate SCF-secreting tumors where they promote tumor growth and induce local immune suppression. SCF R is up-regulated on dendritic cells by Th2-orTh17-biasing stimuli, and it is required for subsequent dendritic cell induction of Th2 and Th17 responses. SCF R protects vascular smooth muscle cells from apoptosis and assists in the recovery of cardiac function following myocardial infarction.

Heparin-binding EGF-like growth factor (HB-EGF) is a 12­16 kDa member of the epidermal growth factor (EGF) family. It possesses an EGF­like domain, and a heparin-binding motif. Mature HB­EGF is a soluble peptide that arises from proteolytic processing of the transmembrane form. Human HB­EGF shows 76% and 73% aa sequence identity with rat and mouse HB­EGF, respectively. It is required for normal cardiac valve formation and normal heart function, promotes smooth muscle cell proliferation. It may be involved in macrophage-mediated cellular proliferation; it is mitogenic for fibroblasts, but not endothelial cells. HB­EGF classified as a group 2 ErbB ligand based on its ability to activate both the EGF/ErbB1 and ErbB4 receptors. Activity associated with ErbB4 binding appears to be limited to non­mitogenic actions, while EGFR binding induces both mitogenic and non­mitogenic activity.

Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus. Plays a role in adipose tissue and glucose Homeostasis in a sex-specific manner. Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells.; In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Regulates mitochondrial respiration activity playing a role in cellular aging. The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates DDX58/RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6.; In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses. Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells.; In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation.; (Microbial infection) In neuronal cells, cell surface-expressed PHB is involved in human enterovirus 71/EV-71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. May serve as a receptor for EV71.

Integrin-linked kinase-associated serine/threonine phosphatase 2C, also known as ILKAP, is a cytoplasm protein that belongs to the PP2C family. ILKAP contains one PP2C-like domain. ILKAP is widely expressed. Highest levels expressed in striated muscle. Much lower levels are evident in various smooth muscle tissues. ILKAP may play a role in the regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation. ILKAP selectively associates with integrin-linked kinase (ILK), to modulate cell adhesion and growth factor signaling. ILKAP inhibits the ILK-GSK3B signaling axis and may play an important role in inhibiting oncogenic transformation. Integrin-linked kinase ( ILK ) plays key roles in a variety of cell functions, including cell proliferation, adhesion, and migration. Within the cell, ILK localizes to multiple sites, including the cytoplasm, focal adhesion complexes that mediate cell adhesion to extracellular substrates, as well as cell-cell junctions in epidermal keratinocytes. Nuclear ILK can be rapidly exported into the cytoplasm through a CRM1-dependent pathway, and its export is enhanced by the type 2C protein phosphatase ILKAP. Nuclear localization of ILK in epidermal keratinocytes is associated with increased DNA synthesis, which is sensitive to inhibition by ILKAP.

Calmodulin (CaM) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of Calmodulin. Once bound to Ca2+, Calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Calmodulin is a small, highly conserved protein that is 148 amino acids long. The protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs (the N- and C-domain) separated by a flexible linker region for a total of four Ca2+ binding sites. Calmodulin mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. Calmodulin is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes, but it is always found intracellularly.

Signal Regulatory Protein α (SIRPα) is a monomeric approximately 90 kD type I transmembrane glycoprotein. The 504 amino acid human SIRPα contains two Ig-like C1-type domains and one Ig-like V-type domain. SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation

Parathyroid hormone (PTH) is a critical hormone in the regulation of Ca++ homeostasis. Parathyroid hormone is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid. This hormone is secreted from cells of the parathyroid glands and finds its major target cells in bone and kidney. Another hormone, parathyroid hormone-related protein, binds to the same receptor as parathyroid hormone and has major effects on development. Like most other protein hormones, parathyroid hormone is synthesized as a preprohormone. After intracellular processing, the mature hormone is packaged with in the Golgi into secretory vesicles, the secreted into blood by exocytosis. In renal epithelium, PTH promotes conversion of Vitamin D to its active form, lowers Ca++ excretion and increases phosphate excretion. PTH also increases hematopoietic stem cell proliferation and mobilization and induces arterial vasodilation by regulating Ca++ influx in PTH1R-expressing arterial smooth muscle.

Hepatoma-Derived Growth Factor is a original member of the HDGF family. HDGF is a cytoplasmic protein and contains one PWWP domain. HDGF expression levels are high in the nucleus and cytoplasm of smooth muscle and endothelial cells. HDGF has proliferative, angiogenic and neurotrophic activity. HDGF was initially characterized as a secreted mitogen from the Huh-7 human hepatoma cell line. As a heparin-binding protein, which is highly expressed in tumor cells where it stimulates proliferation. HDGF has mitogenic activity for fibroblasts and acts as a transcriptional repressor. It has been shown that HDGF is linked with tumorigenesis and the growth of cancer.

SIRPα is a type I transmembrane glycoprotein.It contains two Ig-like C1-type domains and one Ig-like V-type domain. Mouse SIRP alpha ECD shares 61%, 75%, 62%, 61%, and 59% aa sequence identity with human, rat, equine, bovine, and porcine SIRP alpha, respectively.SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation.

Interleukin-13 (IL-13) is a monomeric 17 kDa immunoregulatory cytokine that plays a key role in the pathogenesis of allergy, cancer, and tissue fibrosis. It is secreted by several helper T cell subsets, NK cells, mast cells, eosinophils, basophils, and visceral smooth muscle cells. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. Positively regulates IL31RA expression in macrophages (By similarity).

Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

The cadherin superfamily is a large family that engage in both homo- and heterotypic, calcium-dependent, cell-cell adhesion events, and can be divided into at least four subfamilies based on the extracellular (EC) regions and cytoplasmic domains, that is: classical cadherins, desmosomal cadherins, protocadherins, and cadherin-like molecules. Human cadherin 4, type 1, R-cadherin (retinal), also known as CDH4, CAD4 and RCAD, is a classical cadherin from the cadherin superfamily. It is a calcium-dependent adhesion molecule and a type I transmembrane glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. CDH4 is thought to play an important role during brain segmentation and neuronal outgrowth, and also exerts critical actions in kidney and muscle development. CDH4 is expressed in vascular smooth muscle, pancreatic β-cells, thyroid follicular cells, sensory neurons of the dorsal root ganglia, and, possibly, astrocytes and endothelium of the retina. As a classic cadherin, CDH4 forms both homodimers and heterodimers with N-cadherin. The extracellular region of human CDH4 is 96% aa identical to that of mouse CDH4.

EG-VEGF, also known as prokineticin-1, is a member of the AVIT (prokineticin) family. Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. EG-VEGF can be detected in the steroidogenic glands, ovary, testis, adrenal and placenta. EG-VEGF has little or no effect on a variety of other endothelial and non-endothelial cell types. It induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. It directly influences neuroblastoma progression by promoting the proliferation and migration of neuroblastoma cells. EG-VEGF may play a role in placentation. It may also function in normal and pathological testis angiogenesis. It positively regulates PTGS2 expression and prostaglandin synthesis.

CKB(Creatine kinase B type) contains 1 phosphagen kinase C-terminal domain and 1 phosphagen kinase N-terminal domain. It belongs to the ATP:guanido phosphotransferase family. CKB consists of a homodimer of two identical brain-type CK-B subunits. CKB is a cytoplasmic enzyme involved in cellular energy homeostasis, with certain fractions of the enzyme being bound to cell membranes, ATPases, and a variety of ATP-requiring enzymes in the cell. There, CKB forms tightly coupled microcompartments for in situ regeneration of ATP that has been used up. CKB reversibly catalyzes the transfer of energy-rich phosphate between ATP and creatine or between phospho-creatine (PCr) and ADP. Its functional entity is a homodimer in brain, smooth muscle as well as in other tissues and cells such as neuronal cells, retina, kidney, bone etc.

The eotaxin subfamily of CC chemokines consists of eotaxin-1/CCL11, eotaxin-2/CCL24 and eotaxin-3/CCL26. All eotaxins induce the trafficking of eosinophils to the sites of inflammation via CC chemokine receptor 3 (CCR3), which is also expressed by several different cell types, including basophils, dendritic cells, smooth muscle cells, epithelial cells and fibroblasts. The sequence similarity between the three eotaxins is limited (<4%), but their functional properties are very similar. Eotaxin-1 and -2 are expressed by both haematopoietic and non-haematopoietic cells, but eotaxin-3 expression has been reported to be limited to non-haematopoietic cells. Interleukin (IL)-4 is the main inducer for eotaxin-3 expression, whereas eotaxin-1 is up-regulated by IL-4 and the proinflammatory cytokine tumour necrosis factor (TNF)-α. Eotaxin-3 is expressed in vascular endothelial cells and human dermal fibroblasts after IL-4 and IL-13 stimulation, and this is dependent upon the IL-4-/IL-13-specific transcription factor, signal transducers and activator of transcription (STAT)-6. Eotaxin-3 is expressed on the surface of IL-4-stimulated endothelial cells and promotes eosinophil transmigration.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

C-C Motif Chemokine 3 (MIP-1 alpha,CCL3 ) is a member of the beta or CC subfamily of chemokines and is closely related to CCL4/MIP-1 beta. CCL3 expression can be induced in a variety of hematopoietic cells, fibroblasts, smooth muscle cells, and epithelial cells. Mature mouse CCL3 shares 73%, 91%, and 82% amino acid sequence identity with human, rat, and cotton rat CCL3, respectively. CCL3 exerts its biological functions through interactions with CCR1, CCR3, and CCR5. It is cleared from the extracellular space by internalization via the decoy chemokine receptor D6. CCL3 promotes the chemoattraction, adhesion to activated vascular endothelium, and cellular activation of many hematopoietic cell types including activated T cells, NK cells, neutrophils, monocytes, immature dendritic cells, and eosinophils. CCL3 is also known as stem cell inhibitor (SCI) and can inhibit the proliferation of hematopoietic progenitor cells. CCL3 bioactivity contributes to tumor metastasis and the inflammatory components of viral infection, rheumatoid arthritis, and hepatitis, although it also can suppress the replication of HIV.

Platelet Glycoprotein 4 (CD36) is an integral membrane glycoprotein that has multiple physiological functions. It is broadly expressed on a variety of cell types including microvascular endothelium, adipocytes, skeletal muscle, epithelial cells of the retina, breast, and intestine, smooth muscle cells, erythroid precursors, platelets, megakaryocytes, dendritic cells, monocytes/macrophages, and microglia. As a member of the scavenger receptor family, CD36 is a multiligand pattern recognition receptor that interacts with a large number of structurally dissimilar ligands, including long chain fatty acid (LCFA), advanced glycation end products (AGE), thrombospondin-1,oxidized lowdensity lipoproteins (oxLDLs), high density lipoprotein (HDL), phosphatidylserine, apoptotic cells, β amyloid fibrils (fAβ), collagens I and IV, and Plasmodium falciparuminfected erythrocytes. CD36 is required for the antiangiogenic effects of thrombospondin-1 in the corneal neovascularization assay. It plays a role in lipid metabolism and has been identified as a fatty acid translocase necessary for the binding and transport of LCFA in cells and tissues.

CBFB is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). CBFB is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for CBFB gene. Mutations in CBFB are implicated in cases of breast cancer.

Signal Regulatory Protein α (SIRPα) is a monomeric approximately 90 kD type I transmembrane glycoprotein. The 504 amino acid human SIRPα contains two Ig-like C1-type domains and one Ig-like V-type domain. SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation.

Surfactant Pulmonary-Associated Protein D (SP-D) is a 43 kDa member of the collectin family of innate immune modulators. Its principal components consist of a collagen-like region and a C-terminal carbohydrate recognition domain (CRD), a structure that places it in a subset of pattern recognition proteins termed defense collagens. SP-D is constitutively secreted by alveolar lining cells and epithelium associated with tubular structures and induced in cardiac smooth muscle and endothelial cells. It binds both secreted and transmembrane proteins that transduce its function. It binds human neutrophil defensins, modulating influenza anti-viral defense. It binds MD-2/LY96, a secreted protein that cooperates with Toll-like receptors (TLRs) in the response of macrophages to bacterial lipopolysaccharides (LPS) or cell wall components. It also binds macrophage CD14 and TLRs directly, blocking binding of LPS and down-regulating TNF-α secretion. SP-D binding of both SIRPα and the calreticulin/CD91 complex on macrophages allows for a graded response to environmental challenge.

CD40 Ligand, also known as TNFSF5, CD154, is a type II transmembrane glycoprotein member of the TNF superfamily. Mature mouse CD40 Ligand consists of a 22 amino acid (aa) cytoplasmic domain, a transmembrane segment, and a 214 aa extracellular region. CD40 Ligand is expressed as a homotrimer on platelets and activated T cells and B cells. It is up­regulated following stimulation of basophils, eosinophils, fibroblasts, mast cells, monocytes, natural killer cells, vascular endothelial cells, and smooth muscle cells. CD40 Ligand binds and activates CD40, which is expressed on the surface of B cells, dendritic cells,macrophages, monocytes, platelets, endothelial cells, and epithelial cells. Monomeric, dimeric, and trimeric forms of soluble CD40 Ligand bind to oligomeric CD40 on cell membranes. CD40 ligation by CD40 Ligand promotes B cell activation and T cell­dependent humoral responses. CD40 Ligand dysregulation on T cells and antigen presenting cells contributes to the immune deficiency associated with HIV infection and AIDS. It is also implicated in the pathology of multiple cardiovascular diseases including atherosclerosis, atherothrombosis, and restenosis.

May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells. May suppress inflammation-related signaling in asthmatic airway epithelium. May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism. May play a role in promoting prenatal immune suppression. Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction. Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling. Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity.

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.

Wilms' tumor 1-associating protein (WTAP) was previously identified as a protein associated with Wilms' tumor-1 (WT-1) protein that is essential for the development of the genitourinary system. WT1 was originally identified as a tumor suppressor for Wilms' tumor, but it is also overexpressed in a variety of cancer cells. The WTAP-WT1 axis in vascular cells suggest that WTAP is a vital and multifaceted regulator of vascular remodeling. WTAP has been suggested to function in alternative splicing, stabilization of mRNA, and cell growth. Knocking down endogenous WTAP increased Smooth muscle cells (SMCs) proliferation, because of increased DNA synthesis and G(1)/S phase transition, together with reduced apoptosis. These effects could be the result of WTAP suppressing the transcriptional activity of WT1 in SMCs. WTAP may thus also play a role in messenger RNA processing in mammalian cells, either dependent on or independent of its interaction with WT1.

PDE1C belongs to the cyclic nucleotide phosphodiesterase family, PDE1 subfamily. Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by controlling the rate of their degradation. PDEs are expressed ubiquitously, with each subtype having a specific tissue distribution. These enzymes are involved in many signal transduction pathways and their functions include vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone secretion, immune cell activation, and they are involved in learning and memory. PDE1C has a high affinity for both cAMP and cGMP. It is expressed in several tissues, including brain and heart. As a cyclic nucleotide phosphodiesterase, PDE1C has a dual-specificity for the second messengers cAMP and cGMP.

AIF1, also known as IBA1, is an actin-binding protein. AIF1 is expressed selectively in human macrophage-like cell lines, and in a subset of CD68(+) macrophages in the interstitial and perivascular spaces of human heart allografts. It is expressed in macrophages and neutrophils. AIF1 enhances membrane ruffling and RAC activation. AIF1 enhances the actin-bundling activity of LCP1. It also enhances lymphocyte migration. AIF1 may play a role in macrophage activation and function. It binds calcium and plays a role in RAC signaling and in phagocytosis. It promotes the proliferation of vascular smooth muscle cells and of T-lymphocytes.