Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain that binds ligands; examples include growth factor receptors such as the insulin receptor. To perform signal transduction, RTKs need to form dimers in the plasma membrane; the dimer is stabilized by ligands binding to the receptor. The interaction between the cytoplasmic domains stimulates the autophosphorylation of tyrosine residues within the intracellular kinase domains of the RTKs, causing conformational changes.
signaling pathwayssignaling cascadesignal transduction pathways
A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.
The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. Mutations in TNNI3K are associated to. *
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells, and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.
Amino acids are organic compounds that contain amine (-NH 2 ) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways.
M phasecell cycle progressioncell-cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to duplication of its DNA (DNA replication) and division of cytoplasm and organelles to produce two daughter cells. In bacteria, which lack a cell nucleus, the cell cycle is divided into the B, C, and D periods. The B period extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the splitting of the bacterial cell into two daughter cells.
The structure of ILK consists of three features: 5 ankyrin repeats in the N-terminus, Phosphoinositide binding motif and extreme N-terminus of kinase catalytic domain. Integrins lack enzymatic activity and depend on adapters to signal proteins. ILK is linked to beta-1 and beta-3 integrin cytoplasmic domains and is one of the best described integrins. Although first described as a serine/threonine kinase by Hannigan, important motifs of ILK kinases are still uncharacterized. ILK is thought to have a role in development regulation and tissue homeostasis, however it was found that in flies, worms and mice ILK activity isn’t required to regulate these processes.
NotchNotch signalingNotch receptor
T cell lineage commitment from common lymphoid precursor. regulation of cell-fate decision in mammary glands at several distinct development stages. possibly some non-nuclear mechanisms, such as control of the actin cytoskeleton through the tyrosine kinase Abl. Regulation of the mitotic/meiotic decision in the C. elegans germline. AV boundary formation. Notch signaling can regulate the atrioventricular boundary formation between the AV canal and the chamber myocardium. AV epithelial-mesenchymal transition (EMT). Notch signaling is also important for the process of AV EMT, which is required for AV canal maturation.
interactprotein-protein interactionsprotein-protein interaction
These domains recognize proline enriched sequences, as polyproline type II helical structure (PXXP motifs) in cell signaling proteins like protein tyrosine kinases and the growth factor receptor bound protein 2 (Grb2). Phosphotyrosine-binding (PTB) domain. PTB domains interact with sequences that contain a phosphotyrosine group. These domains can be found in the insulin receptor substrate. LIM domain. LIM domains were initially identified in three homeodomain transcription factors (lin11, is11, and mec3).
transcription factorsgene transcription factortranscriptional factors
components; includes (c-Fos/c-Jun). 1.1.2 Family: CREB. 1.1.3 Family: C/EBP-like factors. 1.1.4 Family: bZIP / PAR. 1.1.5 Family: Plant G-box binding factors. 1.1.6 Family: ZIP only. 1.2 Class: Helix-loop-helix factors (bHLH). 1.2.1 Family: Ubiquitous (class A) factors. 1.2.2 Family: Myogenic transcription factors (MyoD). 1.2.3 Family: Achaete-Scute. 1.2.4 Family: Tal/Twist/Atonal/Hen. 1.3 Class: Helix-loop-helix / leucine zipper factors (bHLH-ZIP). 1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF (USF1, USF2); SREBP (SREBP). 1.3.2 Family: Cell-cycle controlling factors; includes c-Myc. 1.4 Class: NF-1. 1.4.1 Family: NF-1 (A, B, C, X). 1.5 Class: RF-X. 1.5.1 Family: RF-X (1, 2, 3, 4, 5, ANK
ODIN is a member of the ankyrin repeat and sterile alpha motif domain-containing (ANKS) family and contains 6 ankyrin repeats, 1 phosphotyrosine binding (PTD) domain, and 2 tandem sterile alpha motif (SAM) domains. The first SAM domain binds to the SAM domain of the EphA2 receptor by adopting a mid-loop/end-helix conformation and may regulate EphA2 endocytosis. ODIN is widely expressed in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. ODIN has been identified as one of the tyrosine phosphorylated proteins induced by activating epidermal growth factor or platelet-derived growth factor receptor tyrosine kinases.
This protein forms a non-selective calcium-permeable cation channel that is activated by Gαi-coupled receptors, Gαq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico-limbic regions of the brain. In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra. Deletion of the trpc4 gene decreases levels of sociability in a social exploration task.
The active tyrosine kinase phosphorylates specific target proteins, which are often enzymes themselves. An important target is the ras protein signal-transduction chain. Tyrosine kinases recruited to a receptor following hormone binding are receptor-associated tyrosine kinases and are involved in a number of signaling cascades, in particular those involved in cytokine signaling (but also others, including growth hormone). One such receptor-associated tyrosine kinase is Janus kinase (JAK), many of whose effects are mediated by STAT proteins. (See JAK-STAT pathway.)
tyrosine phosphataseprotein tyrosine phosphatasesPTP
Together with tyrosine kinases, PTPs regulate the phosphorylation state of many important signalling molecules, such as the MAP kinase family. PTPs are increasingly viewed as integral components of signal transduction cascades, despite less study and understanding compared to tyrosine kinases. PTPs have been implicated in regulation of many cellular processes, including, but not limited to: PTP activity can be found in four protein families. Links to all 107 members of the protein tyrosine phosphatase family can be found in the template at the bottom of this article.
Lyn (Src family kinase)p56lyn
Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues liver, and adipose tissue. In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor (BCR), CD40, or CD19. The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the Src kinase family. Lyn has been described to have an inhibitory role in myeloid lineage proliferation.
So the use of a tyrosine kinase inhibitor is a possible way of reducing the progression of prostate cancers. A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been developed for therapeutic use. One notable example is dasatinib which has been approved for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (PH+) acute lymphocytic leukemia (ALL). Dasatinib is also in clinical trials for the use in non-Hodgkin’s lymphoma, metastatic breast cancer and prostate cancer. Other tyrosine kinase inhibitor drugs that are in clinical trials include bosutinib, bafetinib, AZD-530, XLl-999, KX01 and XL228.
focal adhesion kinaseFAKfocal adhesion kinase (FAK)
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around). It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility. This gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents.
JAKJAK kinasesJanus Kinases
Tyrosine kinase 2 (TYK2).
ankyrin repeatsANK2ankyrin repeats domain
A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in bipolar disorder. * DARPin (designed ankyrin repeat protein), an engineered antibody mimetic based on the structure of ankyrin repeats * Ankyrin-R Ankyrin-R.
receptor tyrosine kinasestyrosine kinase receptortyrosine kinase receptors
Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non receptor tyrosine kinases which do not possess transmembrane domains. The first RTKs to be discovered were EGF and NGF in the 1960s, but the classification of receptor tyrosine kinases was not developed until the 1970s. Approximately 20 different RTK classes have been identified.
ANNK1 and addictive behaviors
Ankyrin repeat and kinase domain containing 1 (ANKK1) also known as protein kinase PKK2 or sugen kinase 288 (SgK288) is an enzyme that in humans is encoded by the ANKK1 gene. The ANKK1 is a member of an extensive family of the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways. This gene contains a single nucleotide polymorphism that causes an amino acid substitution within the 11th of 12 ankyrin repeats of ANKK1 (Glu713Lys of 765 residues).
Ankyrin-B is a member of the ankyrin family of proteins, and is a modular protein which is composed of three structural domains: an N-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain and death domain; and a C-terminal regulatory domain which is the least conserved and subject to variation, and determines ankyrin-B activity. The membrane-binding region of ankyrin-B is composed of 24 consecutive ankyrin repeats, and it is the membrane-binding domain of ankyrins that confer functional differences among ankyrin isoforms.
It is a protein with 148 amino acids and a molecular weight of 16 kDa that comprises four ankyrin repeats. The name of p16 is derived from its molecular weight, and the alternative name p16 INK4a refers to its role in inhibiting cyclin-dependent kinase inhibitor CDK4. p16 is also known as: * In humans, p16 is encoded by the CDKN2A gene, located on chromosome 9 (9p21.3). This gene generates several transcript variants that differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4.
The main known activity of genistein is tyrosine kinase inhibitor, mostly of epidermal growth factor receptor (EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades. Genistein may act as direct antioxidant, similar to many other isoflavones, and thus may alleviate damaging effects of free radicals in tissues. The same molecule of genistein, similar to many other isoflavones, by generation of free radicals poison topoisomerase II, an enzyme important for maintaining DNA stability. Human cells turn on beneficial, detoxyfying Nrf2 factor in response to genistein insult.