Rabbit light chain 3315, prepared from a homogeneous antipneumococcal antibody, was subjected to hydrolysis by pepsin without prior reduction and alkylation of the intrachain disulfide bonds. Gel filtration of the hydrolysate on Sephadex G-10, G-15, and G-25 and ion exchange chromatography on SP-Sephadex yielded several disulfide bridge peptides. These were fully reduced and alkylated and sequenced by Edman degradation. The peptides were located in the light chain sequence determined in independent studies from our laboratory.. The half-cystine residues in this κB rabbit chain are located at positions 23, 80, 88, 134, 171, 194, and 214. The extra disulfide bridge extends between residues 80 and 171, thus joining the variable and constant domains. This is consistent with x-ray diffraction crystallographic studies showing that the corresponding residues in human light chains are separated by a distance compatible with disulfide bond formation.. ...
The integrity of antibody structure, stability, and biophysical characterization are becoming increasingly important as antibodies receive increasing scrutiny from regulatory authorities. We altered the disulfide bond arrangement of an IgG4 molecule by mutation of the Cys at the N terminus of the heavy chain constant domain 1 (CH1) (Kabat position 127) to a Ser and introduction of a Cys at a variety of positions (positions 227-230) at the C terminus of CH1. An inter-LC-CH1 disulfide bond is thus formed, which mimics the disulfide bond arrangement found in an IgG1 molecule. The antibody species present in the supernatant following transient expression in Chinese hamster ovary cells were analyzed by immunoblot to investigate product homogeneity, and purified product was analyzed by a thermofluor assay to determine thermal stability. We show that the light chain can form an inter-LC-CH1 disulfide bond with a Cys when present at several positions on the upper hinge (positions 227-230) and that such ...
Thiolates, not thiols, attack disulfide bonds. Hence, thiol-disulfide exchange is inhibited at low pH (typically, below 8) where the protonated thiol form is favored relative to the deprotonated thiolate form. (The pKa of a typical thiol group is roughly 8.3, but can vary due to its environment.) Thiol-disulfide exchange is the principal reaction by which disulfide bonds are formed and rearranged in a protein. The rearrangement of disulfide bonds within a protein generally occurs via intra-protein thiol-disulfide exchange reactions; a thiolate group of a cysteine residue attacks one of the proteins own disulfide bonds. This process of disulfide rearrangement (known as disulfide shuffling) does not change the number of disulfide bonds within a protein, merely their location (i.e., which cysteines are bonded). Disulfide reshuffling is generally much faster than oxidation/reduction reactions, which change the number of disulfide bonds within a protein. The oxidation and reduction of protein ...
Correct folding and disulfide bond formation is essential for the function of many secreted proteins including bacterial toxins, and their formation is facilitated by d is ulfide b ond forming (Dsb) oxidoreductase proteins, which usually contain a conserved thioredoxin (TRX) fold [1]. Protein disulfide bonds can serve structural roles, and thus are often buried in the core of a protein. However, in the case of Dsb proteins, partially exposed disulfide bonds in the TRX-fold CXXC motif have catalytic roles in protein folding, electron transport and bioenergetics in a variety of organisms [2, 3].. The Dsb proteins of Escherichia coli are the best characterized, and reside in its periplasm to correctly fold disulfide bond containing secreted and cell-wall proteins [4]. E. coli DsbA (Ec-DsbA) catalyzes the oxidation of disulfide bonds in reduced, unfolded proteins [5, 6], and is then re-oxidized by ubiquinone via E. coli DsbB (Ec-DsbB), an inner membrane transmembrane protein, which in turn is ...
Disulfide bonds play an important role in the folding and stability of many proteins.1-4 For example, S-S bonds are formed following the oxidative folding process between the thiol groups of cysteine, which can also hold different subunits of larger protein complexes together such as antibodies.5 These are also found in keratin in hair.6 In the refining of crude oil, oxidative desulfurization (ODS) of thiols forms the corresponding disulfides7 which then undergo further oxidation to thiosulfinates, disulfoxides, sulfinyl sulfones or disulfones. Disulfides are also used as vulcanizing agents for rubber8 and elastomers,9 in drugs,10 and in the design of rechargeable lithium batteries,11 for example. Traditionally, disulfides are produced through the oxidation of thiols in the presence of homogeneous catalysts including tributylammonium chlorochromate,12 metal phthalocyanines,13 cobalt(II) phthalocyanine tetrasodium sulfonate attached to poly(vinylamine),14 porphyrazinatocobalt(II) complex15 and ...
Protein folding, associated with isomerization of disulfide bonds, was studied using the mixed disulfide between glutathione and reduced ribonuclease T-1 (GS-RNase T-1) as a stable soluble and homogenous starting material; conditions were selected to model those within the lumen of the endoplasmic reticulum where native disulfide bonds are formed in protein biosynthesis, Folding was initiated by addition of free glutathione (GSH +/- GSSG) to promote thiol-disulfide interchange and was monitored by intrinsic protein fluorescence, appearance of native ribonuclease activity, HPLC, and nonreducing SDS-PAGE, All the analyses indicated that native RNase T-1 was recovered in high yield in a variety of redox conditions, Appearance of native activity followed first-order kinetics; kinetic analysis of the intrinsic fluorescence changes indicated an additional rapid process in some conditions, interpreted as the formation of a nonnative intermediate state. Analysis by HPLC and SDS-PAGE also indicated the ...
Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17 or MICU1 (PubMed:16185709, PubMed:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS) (PubMed:16185709, PubMed:19182799, PubMed:21059946). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria (PubMed:16185709, PubMed:19182799, PubMed:21059946). The oxidized form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS (PubMed:16185709, PubMed:19182799, PubMed:21059946). Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system (PubMed:23186364). Mediates formation of disulfide bond in MICU1 ...
Injectable self-healing hydrogels have found broad applications in drug delivery, tissue engineering and controlled 3D cell culture. Recently, cyclic disulfides were found to be useful in cross-linking and stabilizing liposomes by disulfide exchange polymerization, benefiting from the enhanced reactivity of
structure and there are five types. It is these heavy chains which enable antibodies to be separated into the five classes (or isotypes) of immunoglobins; IgG, IgA, IgD, IgM and IgE. The way in which the two heavy chains are connected to one another is through disulfide bonds, they are then connected to a light chain by disulfide bonds as well. This therefore creates two identical antigen-binding sites[4]. The regions of the heavy chain includes three constant domains, which are the same for all antibodies, and the one variable domain. The light chains are also composed of a constant domain and a variable domain. The variable regions of the antibodies are where the antigen binding site is located and the constant domain is responsible for the outcome of the antigen[5]. The Fc region is the part of the antibody that binds to cell surface receptors on cells such as macrophages. Finally, the Fab region is primarily known as the location for the antigen binding site[6]. The domains of antibodies are ...
structure and there are five types. It is these heavy chains which enable antibodies to be separated into the five classes (or isotypes) of immunoglobins; IgG, IgA, IgD, IgM and IgE. The way in which the two heavy chains are connected to one another is through disulfide bonds, they are then connected to a light chain by disulfide bonds as well. This therefore creates two identical antigen-binding sites[4]. The regions of the heavy chain includes three constant domains, which are the same for all antibodies, and the one variable domain. The light chains are also composed of a constant domain and a variable domain. The variable regions of the antibodies are where the antigen binding site is located and the constant domain is responsible for the outcome of the antigen[5]. The Fc region is the part of the antibody that binds to cell surface receptors on cells such as macrophages. Finally, the Fab region is primarily known as the location for the antigen binding site[6]. The domains of antibodies are ...
Human interleukin-12p70 (IL-13) is a 15.8 kDa, glycosylated monomeric cytokine with two internal disulfide bonds. It is secreted by a variety of immune cells. IL-13 is involved in a number of biological processes, such as positive regulation of B-cell proliferation, macrophage activation, immunoglobulin production, protein secretion, and phosphorylation of Stat6 protein. IL-13 initially interacts with IL-13 Rα1 to form a low-affinity complex. The formation of this complex triggers association with IL-4 Rα to form a high-affinity complex that also functions as the type 2 IL-4 receptor complex. IL-13 also binds with high affinity to IL-13 Rα2, which is expressed as a soluble intracellular protein, and also on the cell surface. It is involved in a number of disorders including allergic rhinitis, inflammatory bowel disease, and colorectal cancer. The Human IL-13 Kit provides the assay-specific components for the quantitative determination of endogenous IL-13 in human urine, serum, plasma, and ...
We have devised a generally applicable strategy for analysis of protein structure and have applied it to examine the structure of the transmembrane portion of the Tar receptor of Escherichia coli. The basis of our approach is the use of disulfide cross-linking to identify residues that are within close proximity. To generate and test large numbers of cysteine pairs, we used an unusual method of mutagenesis by which cysteine substitutions can be created randomly at a number of targeted codons. Cysteine-substituted proteins encoded by mutagenized genes may be screened directly for disulfide formation within oligomers or, alternatively, different pools of genes may be randomly recombined to generate gene populations with substitutions in multiple regions. Thus, it is possible to detect a variety of disulfide cross-links between and within individual protein molecules. Interactions between the four membrane-spanning stretches of the Tar dimer were probed by measuring the tendency of 48 cysteine ...
MSD offers a range of individual assays utilizing U-PLEX Antibody Sets that provide a rapid and convenient method for measuring biomarkers in complex matrices. The individual assays are offered on MSD GOLD Small Spot Streptavidin Plates and use the same antibody sets and diluents as the U-PLEX multiplex assays. This allows for efficient transfer between the individual assay and a higher throughput multiplex configuration. Typical of assays developed on the MSD platform, the individual assays have high sensitivity, excellent precision, provide up to five-logs of linear dynamic range, and require minimal sample volume. Interleukin-13 (IL-13) is a glycosylated immunoregulatory cytokine with two internal disulfide bonds. IL-13 is secreted by a variety of immune cells. IL-13 is involved in a number of biological processes, such as positive regulation of B-cell proliferation, macrophage activation, immunoglobulin production, protein secretion, and phosphorylation of Stat6 protein. IL-13 initially ...
Many proteins that are exported from the cytosol pass through a membrane channel into the ER in eukaryotes or the extracellular space in prokaryotes (for reviews see Rapoport et al., 1996; Pohlschroder et al., 1997; Matlack et al., 1998; Johnson and van Waes, 1999). The channel is formed by a heterotrimeric complex of proteins called the Sec61 complex in eukaryotes and the SecY complex in bacteria and archaea. The channel has a hydrophilic interior, as shown by electrophysiology and fluorescence lifetime measurements (Simon and Blobel, 1991; Crowley et al., 1994). Previous models assumed that the channel is formed at the interface between three or four copies of the Sec61/SecY complex (Hanein et al., 1996; Beckmann et al., 1997; Hamman et al., 1997; Manting et al., 2000; Menetret et al., 2000). However, the recently solved X-ray structure of the SecY complex from M. jannaschii is of a monomer with no exterior hydrophilic surfaces in the membrane (van den Berg et al., 2004); thus, the channel ...
1MXP: A New Level of Conotoxin Diversity, a Non-native Disulfide Bond Connectivity in alpha -Conotoxin AuIB Reduces Structural Definition but Increases Biological Activity.
Horseradish peroxidase is used in biochemistry applications such as western blots, ELISA and Immunohistochemistry. It is used to amplify a weak signal and increase detectability of a target molecule, such as a protein. HRP labeled immunoglobulins are used as probes for the demonstration of tissue antigens and in enzyme immunoassay (EIA) systems for determination of soluble and insoluble antigens. HRP is the most desired label for antibodies since it is the smallest and most stable of the three most popular enzyme labels (HRP, alkaline phosphatase, and B-galactosidase) and its glycosylation leads to lower non-specific binding. It is also useful for tracing neural connections. These include motor and sensory innervation of peripheral organs, and connections of peripheral nerves, ganglia and individual dorsal roots. HRP can be conjugated to antibodies by several different methods including glutaraldehyde, periodate oxidation, through disulfide bonds, and also via amino and thiol directed ...
A major finding of our present study is that integrin α4β7 can be activated by selectively breaking two conserved disulfide bonds, α4C589-C594 and β7C494-C526, located at the knees of integrin. Interestingly, integrin activated by this mechanism has a unique active conformation that is different from the global conformation induced by Mn2+ stimulation. In addition, activated α4β7 integrin can spontaneously cluster on the cell membrane and trigger integrin outside-in signaling independent of ligand binding.. All integrins contain a large number of disulfide bonds that are generally believed to facilitate protein folding and stabilize three-dimensional structures (Calvete et al., 1991). The two disulfide bonds at the knees of integrin α4β7 are exposed to solution, making them easily accessible to reducing agents. In this study, these two disulfide bonds were selectively reduced by 0.1 mM DTT, which induced the activation of integrin α4β7 and triggered outside-in signaling. Accumulating ...
Sigma-Aldrich offers abstracts and full-text articles by [Martha N Calderon, Carlos A Guerrero, Orlando Acosta, Susana Lopez, Carlos F Arias].
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Immunoglobulin heavy-chain binding protein (BiP, GRP-78) associates tightly in the endoplasmic reticulum (ER) with newly synthesized proteins that are incompletely assembled, have mutant structures, or are incorrectly glycosylated. The function of BiP has been suggested to be to prevent secretion of incorrectly folded or incompletely assembled protein, to promote folding or assembly of proteins, or to solubilize protein aggregates within the ER lumen. Here we examine the interaction of BiP with newly synthesized polypeptides in an in vitro protein translation-translocation system. We find that BiP forms tight complexes with nonglycosylated yeast invertase and incorrectly disulphide-bonded prolactin, but does not associate detectably with either glycosylated invertase or correctly disulphide-bonded prolactin. Moreover, BiP associates detectably only with completed chains of prolactin, not with chains undergoing synthesis. We conclude that BiP recognizes and binds with high affinity in vitro to ...
Bacterial growth and pathogenicity depend on the correct formation of disulfide bonds, a process controlled by the Dsb system in the periplasm of Gram-negative bacteria. Proteins with a thioredoxin fold play a central role in this process. A general feature of thiol-disulfide exchange reactions is the need to avoid a long lived product complex between protein partners. We use a multidisciplinary approach, involving NMR, x-ray crystallography, surface plasmon resonance, mutagenesis, and in vivo experiments, to investigate the interaction between the two soluble domains of the transmembrane reductant conductor DsbD. Our results show oxidation state-dependent affinities between these two domains. These observations have implications for the interactions of the ubiquitous thioredoxin-like proteins with their substrates, provide insight into the key role played by a unique redox partner with an immunoglobulin fold, and are of general importance for oxidative protein-folding pathways in all organisms.
Laminins [(PUBMED:2404817)] are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation. They are composed of distinct but related alpha, beta and gamma chains. The three chains form a cross-shaped molecule that consist of a long arm and three short globular arms. The long arm consist of a coiled coil structure contributed by all three chains and cross-linked by interchain disulphide bonds. Beside different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines [(PUBMED:2666164)]. The tertiary structure [(PUBMED:8648630), (PUBMED:8648631)] of this domain is remotely similar in its N-terminal to that of the EGF-like module. It is known as a LE or laminin-type EGF-like domain. The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found. A schematic ...
Laminins [(PUBMED:2404817)] are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation. They are composed of distinct but related alpha, beta and gamma chains. The three chains form a cross-shaped molecule that consist of a long arm and three short globular arms. The long arm consist of a coiled coil structure contributed by all three chains and cross-linked by interchain disulphide bonds. Beside different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines [(PUBMED:2666164)]. The tertiary structure [(PUBMED:8648630), (PUBMED:8648631)] of this domain is remotely similar in its N-terminal to that of the EGF-like module. It is known as a LE or laminin-type EGF-like domain. The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found. A schematic ...
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Citation: Meng, Y., Moscou, M., Wise, R.P. 2008. Blufensin1 Negatively Impacts Basal Defense in Response to Barley Powdery Mildew. Plant Physiology. 149(1):271-285. Interpretive Summary: Plant diseases are among the greatest deterrents to crop production worldwide. Pathogenic fungi, viruses, bacteria, insects, and nematodes impact agronomic and horticultural crops, as well as commercial and recreational forests. ARS researchers have isolated a novel regulator of disease defense. The new monocot-specific gene encodes a family of small cysteine-rich peptides, designated blufensins. BLUFENSIN1 (BLN1) is highly induced during infection by pathogenic fungi and contains both structural and sequence similarities to knottins, a diverse family of small disulfide-rich proteins characterized by a unique disulfide through disulfide knot. This discovery, also supported by the National Science Foundation-Plant Genome Research Program, establishes a previously unrecognized role for small peptides as negative ...
Sephiroth 20140618 :: DESCRIPTION Sephiroth is a disulfide connectivity pattern predictor based on evolutionary information retrieved from Multiple Sequence Alignments (MSAs). ::DEVELOPER (IB)² - Interuniver
Disulfide bridges are an important structural element in many proteins and peptides. This brochure is a guideline how to plan and execute the synthesis of peptides with one or several disulfide bridges.
1MDK: Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B.
colored in yellow) [6] [7] [8] [9]. One structural feature of Pin-II IRD is a disordered loop with triple stranded β sheet scaffold. The disordered solvent exposed reactive loop is anchored by the four conserved disulfide bonds (C4-C41, C7-C25, C8-C37 and C14-C50) [10] [11]. Among the four disulfide bonds, C8-C37 has been found to be very crucial for maintaining active conformation, whereas C4-C41 has an important role in maintaining the flexibility of the reactive loop [12]. Thus, any selective loss of disulfide bond is expected to have evolutionary significance leading to functional differentiation of inhibitors [13]. [A] Functionality: To assess the effect of aa variations on activity and structural stability different biochemical studies and 20 ns MD simulations was performed on IRD structures. Inhibition kinetic studies displayed a sigmoidal pattern with increasing concentrations of the inhibitors suggesting reversible and competitive inhibition with tight binding. IRD-9 turned out to be a ...
The meeting was introduced by P. Pontarotti (Marseille, France), who discussed the evolutionary genetics of the MHC based on the ideas of gene co‐option and exon shuffling as the drivers of new functions for existing structures. These ideas about the evolution of the MHC suggest that conserved regions brought into new structures could retain their old (binding) functions. N. Bulleid (Manchester, UK) introduced the topic of MHC class I biosynthesis, describing a semi‐permeable cell system with an intact endoplasmic reticulum that allowed him to address the timing and partners involved in the formation of disulphide bonds between MHC class I and endoplasmic reticulum molecules. He also emphasized the role of the endoplasmic reticulum redox environment and the importance of a transmembrane cysteine residue in associating nascent class I molecules with their appropriate partners. This talk connected to later talks that highlighted misfolding and aberrant disulphide‐bond formation in disease. ...
I didnt even use oxidative environment to trigger disulfide bond formation. Only 1xPBS incubation for 30 min at room temperature, then I saw the dimer on western blot.....Of course this dimer also appears in oxidative enviroment group, but since I can get it using PBS, why bother using oxidative agents?....Afterwards I found out that this dimer doesnt break at RT with DTT or ME, and does break when boiling without DTT ...
Principal Investigator:SHIRATANI Masaharu, Project Period (FY):2009-07-23 - 2014-03-31, Research Category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Project Area:Creation of Science of Plasma Nano-Interface Interactions
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(H-Cys-ala-oh)2,(disulfide bond)/ACM20898219 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
H-Ala-cys-ser-ser-ser-pro-ser-lys-his-cys-gly-oh,(disulfide bond)/ACM888486235 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
✅ Question: Which statement is true? A. a molecule having a covalent bond can be ionic B. a molecule having a covalent bond is always polar C. a molecule having a covalent bond may be polar or nonpolar D. a molecule having a covalent bond i =s always nonpolar
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The very excellent Dr Clive Metcalfe (an ex-post-doc with me) of NIBSC has a PhD project with Prof Paul Dalby at UCL looking at disulphide bond reduction in monoclonal antibodies ...
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Encourage interaction within the local institute to start building relationships between students in different years of the program. Stronger bonds form when students see each other on a daily basis around campus and once they are established, these bonds can carry over between institutes ...
Double Bond Formation video This Scientific content most probably shows video related to topic: Double Bond Formation. However in few cases, video content could be different than the title.
Most bridges are built to stay in place, enhancing their durability and ensuring they help people tackle challenging terrains. Drawbridges are an exception, with some disconnecting at the mid
Assume that you can buy a bond for $555 today. The bond will pay you $75 in annual coupon payments (i.e. interest payments) at the end of each of the next 12 years, plus repay the original $1000 par value of the bond at the end.
Product Number: C6228 CAS number: 47931-85-1 Synonyms: L-Cysteinyl-L-seryl-L-asparaginyl-L-leucyl-L-seryl-L-threonyl-L-cysteinyl-L-valyl-L-leucylglycyl-L-lysyl-L-leucyl-L-seryl-L-glutaminyl-L-alpha-glutamyl-L-leucyl-L-histidyl-L-lysyl-L-leucyl-L-glutaminyl-L-threonyl-L-tyrosyl-L-prolyl-L-arginyl-L-threonyl-L-asparaginyl-L-threonylglycyl-L-serylglycyl-L-threonyl-L-prolinamide, cyclic(1-7)-disulfide. ...
J. DAVID SCHOFIELD, JOUNI J. UITTO, DARWIN J. PROCKOP; Interchain Disulphide Bonding in Procollagen from Embryonic Chick Tendon Cells and the Formation of the Triple-Helical Structure. Biochem Soc Trans 1 February 1974; 2 (1): 90-93. doi: https://doi.org/10.1042/bst0020090. Download citation file:. ...
Human serum albumin (HSA) nanoparticles stabilized with intermolecular disulfide bonds Wentan Wang, Yanbin Huang*, Shufang Zhao, Ting Shao and Yi Cheng* Department of Chemical Engineering, Tsinghua University,
Bridging Small Molecules to Modified Bacterial Microparticles Using a Disulphide Linkage: MIS416 as a Cargo Delivery System. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
About the Poster: Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1l has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1k. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1l and human IgG1k were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this ...
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages ...