Search results

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.

MARCKS-related protein (MARCKSL1) which is a part of MARCKS family of PKC substrate is broadly used in the signal transduction studies as an indicator of PKC activation. MARCKSL1 plays a part in the coordination of membrane-cytoskeletal signaling events, including secretion, migration, phagocytosis and cell adhesion and is expressed in a variety of tissues with highest levels found in testis and uterus. Furthermore, MARCKSL1 serves as a regulator of Integrin activation and is thought to regulate Integrin-dependent signal transduction pathways, particularly those involved in macrophage spreading.

PKLR is a pyruvate kinase which catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP. That is the rate-limiting step of glycolysis. PKLR gene encodes the L- and R-type isoenzymes through alternate splicing events controlled by different promoters. L-type isoform can also appear as a tetramer and is upregulated by glucose with implications in maturity-onset diabetes of the young.

Protein-c Receptor (PROCR) is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The PROCR protein is an N-glycosylated type I membrane protein which enhances the activation of protein C. PROCR gene mutations are linked with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. In addition, PROCR may have a role in malarial infection and has been linked with cancer.

Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2) which is mostly expressed in mesenchymal cells is a part of the discoidin-like domain containing subfamily of receptor tyrosine kinases. DDR2 whose ligand is fibrillar collagen rather than a growth factor-like peptide is unique among RTKs. DDR2 regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. DDR2 is also essential for normal bone development.

TPMT, thiopurine S-methyltransferase, is a cytosolic enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. TPMT activity exhibits autosomal codominant genetic polymorphism, and patients inheriting TPMT-deficiency are at high risk of potentially fatal hematopoietic toxicity.

TIE1 is an angiopoitein receptor which takes part in hematopoiesis,angiogenesis and vasculogenesis.TIE1 is expressed primarily on endothelial and hematopoietic progenitor cells. TIE1 is expressed in immature hematopoietic Recombinant Human TIE1 protein cells and platelets. TIE1 upregulates the cell adhesion molecules(CAMs) VCAM-1,ICAM-1 and E-selectinthrough a p38-dependent mechanism. TIE1 has a proinflammatory effect and takes part in the endothelial inflammatory diseases such as atherosclerosis.

Nuclear distribution gene C homolog (NUDC) is a nuclear distribution protein. The NUDC protein has a key role in mitosis and cytokinesis. NUDC is involved in spindle formation during mitosis and in microtubule organization during cytokinesis. NUDC is required for correct formation of mitotic spindles and chromosome separation during mitosis, as well as cell proliferation. NUDC also has a role in neurogenesis and neuronal migration.

Protein-c Receptor (PROCR) is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The PROCR protein is an N-glycosylated type I membrane protein which enhances the activation of protein C. PROCR gene mutations are linked with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. In addition, PROCR may have a role in malarial infection and has been linked with cancer.

STAT1 is a member of the Signal Transducers and Activators of Transcriptionfamily of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type Ior type IIinterferons. In response to IFN-?stimulation, STAT1 forms homodimers or heterodimers with STAT3that bind to the GAS (Interferon-Gamma Activated Sequence) promoter element; in response to either IFN-? or IFN-?stimulation, STAT1 forms a heterodimer with STAT2that can bind the ISRE (Interferon Stimulated Response Element) promoter element. In either case, binding of the promoter element leads to an increased expression of ISG (Interferon Stimulated Genes).

Fibroblast Growth Factors (FGFs) comprise a family of at least 18 structurally related proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentiation, angiogenesis, wound healing and tumorigenesis. The biological activities of the FGFs are mediated by a family of type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). An IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

KLRC2 has a part as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. The group, designated KLRC (NKG2) are expressed mainly in natural killer (NK) cells and encodes a family of transmembrane proteins categorized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The KLRC (NKG2) gene family is situated inside the NK complex, a region which holds a few C-type lectin genes specially expressed on NK cells. KLRC2 alternative splice variants are known but their full-length nature is yet to be determined.

Troponin-C2 (Troponin C, skeletal muscle) is the central regulatory antigen of striated muscle contraction, and modulates the Ca2+-activation characteristics of muscle fibers. Troponin-C2 has three subunits, Troponin I(Tn-1), Troponin T(Tn-T) and Troponin C(Tn-C). Tn-I subunit inhibits actomyosin ATPase and Tn-T subunit binds tropomyosin and Tn-C, while Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. Mutations in all components of this complex have been linked with skeletal muscle disease.

Proprotein Convertase Subtilisin/Kexin Type 1 Inhibitor (PCSK1N) takes part in the control of the neuroendocrine secretory pathway. PCSK1N inhibits prohormone convertase 1, which regulates the proteolytic cleavage of neuroendocrine peptide precursors. PCSK1Nslows down convertase-mediated processing of proopiomelanocortin and proenkephalin and also monitors the intracellular timing of PCSK1.

HER-2/neu (erbB-2) encodes an 185-kDa orphan receptor tyrosine kinase that is constitutively active as a dimer and displays potent oncogenic activity when overexpressed. Herstatin, as the product of alternative HER-2 transcript, retains intron 8.
The herstatin mRNA is expressed in normal human fetal kidney and liver, but is at reduced levels relative to p185HER-2 mRNA in carcinoma cells that contain an amplified HER-2 gene. Herstatin appears to be an inhibitor of p185HER-2, because it disrupts dimers, reduces tyrosine phosphorylation of p185, and inhibits the anchorage-independent growth of transformed cells that overexpress HER-2.

Glycophorin C, also known as GYPC, is an integral membrane glycoprotein. GYPC is a minor species which is carried by human erythrocytes, however plays an important role in regulating the mechanical stability of red cells. Numeral glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 & 2, respectively. The Webb & Duch antigens, also identified as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very slight homology with glycophorins A & B.

The Casein kinase 2 (EC2.7.11.1) is a serine/threonine-selective protein kinasethat is a tetramer of two alpha subunits and two beta subunits. The alpha subunits have the catalytic kinase domain. Casein kinase 2 has been implicated in cell cyclecontrol, DNA repair, regulation of the circadian rhythmand other cellular processes.
Casein kinase 2 activity has been reported to be activated following Wnt signaling pathwayactivation. A Pertussis toxin-sensitive G proteinand Disheveled appear to be an intermediary between Wnt-mediated activation of the Frizzled receptor and activation of casein kinase 2.
Mice that lack casein kinase 2 alpha prime have a defect in the morphology of developing sperm.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms that have been identified in mammals. The 14-3-3gamma, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

NELL2 is expressed in large quantities in neural tissues and has a significant role in the development of neural tissues. In addition, NELL protein has six epidermal growth factor (EGF)-like repeat domains which plays a part in calcium binding.

Inositol Hexakisphosphate Kinase 2 (IP6K2) which is a part of the inositol IPK family converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate. IP6K2 also converts 1, 3, 4, 5, 6-pentakisphosphate (InsP5) to PP-InsP4. IP6K2 is a protein coding gene which suppresses the growth and affects the apoptotic activities of IFN-beta in several ovarian cancers.

Cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2) is a member of the peptidase M16 family. UQCRC2 is a component of the ubiquinol-cytochrome c reductase complex (complex III), which is a part of the mitochondrial respiratory chain. UQCRC2 is essential for the compilation of the complex.

AURKA (Aurora Kinase A) belongs to the mitotic serine/threonine kinases family. AURKA is a cell cycle-regulated kinase which may be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. AURKA is found at the centrosome in interphase cells and at the spindle poles in mitosis. Since the AURKA expression is cell-cycle regulated, it is low in G1/S, it accumulates during G2/M, and it decreases rapidly after. AURKA is involved in important processes during mitosis and meiosis whose proper function is essential for healthy cell proliferation. In addition, AURKA plays an essential role in tumourigenesis and is overexpressed in various types of cancers. AURKA is strongly expressed in the testis, colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines and weakly in skeletal muscle, thymus and spleen. AURKA interacts with its substrates BORA and ARHGEF2, as well as with TACC1 and CPEB1.
Defects in the AURKA gene cause numerical centrosome aberrations including aneuploidy. AURKA overexpression has been linked to chromosomal instability in colorectal cancer. AURKA expression may have a prognostic significance in ovarian carcinoma.

Streptokinase is an extracellular metallo-enzymeproduced by beta-haemolytic streptococcusand is used as an effective and cheap clot-dissolving medicationin some cases of myocardial infarction(heart attack) and pulmonary embolism.
It belongs to a group of medications known as fibrinolytics, and works by activating plasminogenthrough cleavage to produce plasmin.