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Signal-regulatory Protein Alpha
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons. SIRPα acts as inhibitory receptor and interacts with a broadly expressed transmembrane protein CD47 also called the "don't eat me" signal. This interaction negatively controls effector function of innate immune cells such as host cell phagocytosis. SIRPα diffuses laterally on the macrophage membrane and accumulates at a phagocytic synapse to bind CD47 and signal 'self', which inhibits the cytoskeleton-intensive process of phagocytosis by the macrophage. This is analogous to the self signals provided by MHC class I molecules to NK cells via Ig-like or Ly49 receptors. NB. Protein shown to the right is CD47 not SIRP α. Structure The cytoplasmic region of SIRPα is highly conserved between rats, mice and humans. Cytoplasmic region contains a number of tyrosine residues, which likely act as ITIMs. Upon CD47 ligation, S ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD47
CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 ( TSP-1) and signal-regulatory protein alpha ( SIRPα). CD-47 acts as a ''don't eat me'' signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis. CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. Furthermore, it plays a key role in immune and angiogenic responses. CD47 is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells. Expression in equine cutaneous tumors has been reported as well. Structure CD47 is a 50 kDa membrane receptor that has extracellular N-te ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PTPN11
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the ''PTPN11'' gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migrati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SREBP
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes '' SREBF1'' and ''SREBF2''. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop. Isoforms Mammalian genomes have two separate SREBP genes ( and ): * SREBP-1 expression produces two different isoforms, SREBP-1a and -1c. These isoforms differ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PTPN6
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' gene. Function The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog ( SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling, (e.g., the LYN-CD22- SHP-1 pathway). Multiple ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Surfactant Protein D
Surfactant protein D, also known as SP-D, is a lung surfactant protein part of the collagenous family of proteins called collectin. In humans, SP-D is encoded by the ''SFTPD'' gene and is part of the innate immune system. Each SP-D subunit is composed of an N-terminal domain, a collagenous region, a nucleating neck region, and a C-terminal lectin domain. Three of these subunits assemble to form a homotrimer, which further assemble into a tetrameric complex. Interactions Surfactant protein D has been shown to interact with DMBT1, and hemagglutinin of influenza A virus. Post-translational modification of SP-D i.e. S-nitrosylation switches its function. See also * pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-water in ... References Further reading * * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Surfactant Protein A
Surfactant protein A is an innate immune system collectin. It is water-soluble and has collagen-like domains similar to SP-D. It is part of the innate immune system and is used to opsonize bacterial cells in the alveoli marking them for phagocytosis by alveolar macrophages. SP-A may also play a role in negative feedback limiting the secretion of pulmonary surfactant. SP-A is not required for pulmonary surfactant to function but does confer immune effects to the organism. During parturition The role of surfactant protein A (SP-A) in childbirth is indicated in studies with mice. Mice which gestate for 19 days typically show signs of SP-A in amniotic fluid at around 16 days. If SP-A is injected into the uterus at 15 days, mice typically deliver early. Inversely, an SP-A inhibitor injection causes notable delays in birth. The presence of surfactant protein A seemed to trigger an inflammatory response in the uterus of the mice, but later studies found an anti-inflammatory response in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Pathways Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and phagocytosis. * Clathrin-mediated endocytosis is mediated by the production of small (approx. 100 nm in diameter) vesicles that have a morphologically characteristic coat made up of the cytosolic protein clathrin. Clathrin-coated vesicles (CCVs) are found in virtually all cells and form domains of the plasma membrane ter ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunoglobulin Superfamily
The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins (also known as antibodies); they all possess a domain known as an immunoglobulin domain or fold. Members of the IgSF include cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system, molecules involved in antigen presentation to lymphocytes, cell adhesion molecules, certain cytokine receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. Otherwise, the sperm-specific protein IZUMO1, a member of the immunoglobulin superfamily, has also been identified as the only sperm membrane protein essential for sperm-egg fusion. Immunoglobulin domains Proteins of the IgSF possess a structural domain ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunoreceptor Tyrosine-based Inhibitory Motif
An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family found on immune cells. These immune cells include T cells, B cells, NK cells, dendritic cells, macrophages and mast cells. ITIMs have similar structures of S/I/V/LxYxxI/V/L, where x is any amino acid, Y is a tyrosine residue that can be phosphorylated, S is the amino acide Serine, I is the amino acid Isoleucine, and V is the amino acid Valine. ITIMs recruit SH2 domain-containing phosphatases, which inhibit cellular activation. ITIM-containing receptors often serve to target Immunoreceptor tyrosine-based activation motif(ITAM)-containing receptors, resulting in an innate inhibition mechanism within cells. ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of the immune re ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Innate Immune System
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).. The major functions of the innate immune system are to: * recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines * activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells * identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells * activate the adaptive immune system through antigen presentation * act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures suc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek ''tyrós'', meaning '' cheese'', as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is encoded by the codons UAC and UAU in messenger RNA. Functions Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes and functions as a receiver of phosphate groups that are transferred by way of protein kinases. Phosphorylation of the hydroxyl group can change the activity of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ly49
Ly49 is a family of membrane C-type lectin-like receptors expressed mainly on NK cells but also on other immune cells (some CD8+ and CD3+ T lymphocytes, intestinal epithelial lymphocytes (IELs), NKT cells, uterine NK cells (uNK) cells, macrophages or dendritic cells). Their primary role is to bind MHC-I molecules to distinguish between self healthy cells and infected or altered cells. Ly49 family is coded by Klra gene cluster and include genes for both inhibitory and activating paired receptors, but most of them are inhibitory. Inhibitory Ly49 receptors play a role in the recognition of self cells and thus maintain self-tolerance and prevent autoimmunity by suppressing NK cell activation. On the other hand, activating receptors recognise ligands from cancer or viral infected cells (induced-self hypothesis) and are used when cells lack or have abnormal expression of MHC-I molecules (missing-self hypothesis), which activate cytokine production and cytotoxic activity of NK and immune ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
