Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cyclin D1 has been associated with a wide variety of proliferative diseases but its biochemical role is unknown. In diploid fibroblasts we find that cyclin D1 is complexed with many other cellular proteins. Among them are protein kinase catalytic subunits CDK2, CDK4 (previously called PSK-J3), and CDK5 (also called PSSALRE). In addition, polypeptides of 21 kd and 36 kd are identified in association with cyclin D1. We show that the 36 kd protein is the proliferating cell nuclear antigen, PCNA. Cyclin D3 also associates with multiple protein kinases, p21 and PCNA. It is proposed that there exists a quaternary complex of D cyclin, CDK, PCNA, and p21 and that many combinatorial variations (cyclin D1, D3, CDK2, 4, and 5) may assemble in vivo. These findings link a human putative G1 cyclin that is associated with oncogenesis with a well-characterized DNA replication and repair factor.
 ...
PMID:D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. 135 58

The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.
 ...
PMID:Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. 138 15

VirA and VirG activate the Agrobacterium tumefaciens vir regulon in response to phenolic compounds, monosaccharides, and acidity released from plant wound sites. VirA contains an amino-terminal periplasmic domain and three cytoplasmic domains: a linker, a protein kinase, and a phosphoryl receiver. We constructed internal deletions of virA that truncate one or more domains and tested the ability of the resulting proteins to mediate environmentally responsive vir gene activation in vivo. The periplasmic domain is required for sensing of monosaccharides (in agreement with earlier results), while the linker domain is required for sensing of phenolic compounds and acidity. The phosphoryl receiver domain of VirA plays an inhibitory role in signal transduction that may be modulated by phosphorylation. The carboxy terminus of the protein was also dispensable for tumorigenesis, while the periplasmic domain was required.
 ...
PMID:Functional roles assigned to the periplasmic, linker, and receiver domains of the Agrobacterium tumefaciens VirA protein. 140 Feb 53

We recently derived a GnRH-responsive pituitary cell line of the gonadotrope lineage (alpha T3-1) by targeted oncogenesis in transgenic mice. Here, we report studies characterizing the GnRH receptors present in these cells and the intracellular responses to GnRH treatment. The receptors in alpha T3-1 cells show specificity for different GnRH analogs, with dissociation constants very similar to those found in normal rat and mouse pituitary. The concentration of receptors is within the range found in normal pituitary. The addition of GnRH or GnRH agonists increases phosphoinositide turnover and protein kinase-C translocation to membranes, and enhances activation of voltage-sensitive calcium channels. However, GnRH does not affect cAMP levels. Analysis of alpha-subunit mRNA levels demonstrated induction by GnRH and phorbol esters. Our results indicate that GnRH initiates a cascade of intracellular events that generate a set of second messengers, one or more of which is involved in the regulation of gene expression. The responses of alpha T3-1 cells to GnRH appear to have characteristics equivalent to those of primary pituitary gonadotropes, indicating the utility of this cell line as a model system for the study of GnRH responses.
 ...
PMID:Intracellular responses to gonadotropin-releasing hormone in a clonal cell line of the gonadotrope lineage. 165 91

p34cdc2 is a protein kinase that has an important role in controlling cell cycle progression and may regulate tumor suppressor gene activity. In this work, we show that the arrest of cell growth and induction of differentiation in a tumorigenic neuroblastoma cell line by retinoic acid (RA) is associated with a 75-fold decrease in the level of p34cdc2 protein. The RA induced decrease in p34cdc2 levels does not simply reflect the arrest of cell growth, because p34cdc2 levels are not reduced when neuroblastoma cells are growth arrested by nutrient deprivation. Furthermore, dephosphorylation of the tumor suppressor gene product RB, a substrate for the p34cdc2 kinase activity, is observed only when p34cdc2 levels are decreased in RA treated cells. These studies link regulation of cdc2 level, RB phosphorylation state, and induction of differentiation by RA and suggest that alterations in the cdc2 gene or in genes controlling its regulation contribute to tumorigenesis.
 ...
PMID:Retinoic acid negatively regulates p34cdc2 expression during human neuroblastoma differentiation. 175 5

Crown gall tumorigenesis by Agrobacterium tumefaciens requires the co-ordinate transcriptional induction of a set of pathogenesis genes. At least three classes of environmental stimuli act synergistically to induce these genes: (i) monocyclic aromatic hydrocarbons such as acetosyringone, coniferyl alcohol, and vanillin, (ii) neutral or acidic monosaccharides such as glucose and glucuronic acid, and (iii) acidic pH. Three proteins are required to sense and respond to these stimuli: (i) VirA, a transmembrane sensory protein and histidine protein kinase, (ii) VirG, a transcriptional activator which is phosphorylated by phosphoryl VirA, and (iii) ChvE, a periplasmic sugar-binding protein. VirA and VirG are members of the so-called two-component family of regulatory proteins. This regulatory system continues to offer new discoveries in the areas of signal transduction, host-microbe interactions, and host range.
 ...
PMID:An Agrobacterium two-component regulatory system for the detection of chemicals released from plant wounds. 179 50

One of the most fundamental questions in biology is how a cell is able to regulate its division cycle. Initially it was thought that in mammalian cells control over entry into the cell cycle is exerted at a restriction point in G1; once past this point the cell would be free to undergo all the steps needed until the following division. Hence, for many years research on tumorigenesis focused on the mitogenic activation of quiescent cells by growth factors, peptide hormones and oncogene products (for reviews see [1, 2]). These studies investigated the initial steps required to induce a quiescent, nondividing cell to proliferate, and led to the identification of many growth factor receptors, of both the tyrosine kinase family and the G-protein coupled family. Receptors bearing protein tyrosine phosphatase or serine kinase catalytic domains were also identified via this route (for reviews see [3, 4, 5]). However more recent studies on the cooperation between different growth factors for mitogenesis have shown that multiple requirements exist for a cell to proceed through the entire division cycle. Indeed studies in several different organisms, pioneered by investigators working with Ascomycetes [6, 7, 8], have now clearly shown that the eukaryotic cell cycle proceeds through multiple check-points. Furthermore, it now appears that many of the regulatory elements and even pathways have been conserved throughout evolution. In this review we discuss the possible involvement of one of the transducing molecules, cyclin A, in abnormal cell proliferation.
 ...
PMID:Cyclin A, cell cycle control and oncogenesis. 183 23

How does a quiescent cell decide to re-enter the cell cycle and start replicating its DNA? What controls cell proliferation? These are fundamental questions that have to be solved in order to understand the mechanisms of oncogenesis. Some recent data have provided clues about how signal transduction pathways may be connected to the cell cycle. A protein kinase cascade starting from the membrane growth factor receptor is thought to be involved in transducing extracellular stimuli to the master switches of the cell cycle control machinery. The recently identified extracellular-signal regulated kinases (ERKs) appear to play an important role in this pathway. Expression of cyclins, which are regulatory subunits of the universal cell cycle oscillator cdc2, may also be controlled through this kinase cascade. The products of tumor suppressor genes Rb and p53 also play an important role in regulating cell proliferation by interfering with the cell cycle pathway. Here, I will review and discuss the importance of these different new results.
 ...
PMID:From growth to cell cycle control. 184 42

An hypothesis has been presented suggesting that two isoforms of cAMP receptor proteins are crucial effectors in tumorigenesis. The evidence in support of this hypothesis shows that: (1) cAMP transduces dual controls, both positive and negative, on cell growth and differentiation. (2) Such dual controls are respectively governed by two isoforms of cAMP receptor proteins, the type I and type II regulatory subunits of cAMP-dependent protein kinase. (3) In normal physiology, the functional balance of these cAMP receptor isoforms is strictly controlled to meet either stimulation or inhibition of cell growth as it is required, whereas such control is lost in cancer cells. (4) Cancer cells can also be made to differentiate and acquire growth control when the functional balance of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs, antisense strategy, or gene transfer, suggesting new approaches to cancer therapy.
 ...
PMID:Suppression of malignancy targeting the intracellular signal transducing proteins of cAMP: the use of site-selective cAMP analogs, antisense strategy, and gene transfer. 184 39

The mechanisms that restrict cell proliferation play an important regulatory role in differentiation and tumorigenesis. The growth of PRL-secreting cells of the anterior pituitary is known to be highly estrogen dependent; however, estrogen may act indirectly via growth regulatory polypeptides. We have used the GH4C1 rat pituitary cell line to investigate the action of two classes of growth regulatory polypeptides, transforming growth factor-alpha (TGF alpha) and TGF beta. TGF alpha and TGF beta each inhibit GH4 cell proliferation, as measured by cell number and [3H]thymidine incorporation, and given together arrest GH4 cell proliferation. The growth inhibitory action of TGF alpha is concentration dependent (IC50 = 100 pM) and saturable. Activin-A, a TGF beta-related polypeptide, also inhibits proliferation, but is less effective than TGF beta. TGF alpha and TGF beta each alter GH4 cell cycle distribution by decreasing in the percentage of S phase cells (74% and 34%, respectively) and increasing proportionally G0-G1 phase cells. The growth inhibitory action of TGF alpha differs from that of TGF beta in that TGF alpha also causes a temporary accumulation of cells in G2-M phases. We next initiated experiments to evaluate the role of protein kinase-C in the growth inhibitory actions of TGF alpha and TGF beta. The alpha- and beta-isoforms of protein kinase-C were down-regulated by pretreatment with 12-O-tetradecanoylphorbol-13-acetate, yet TGF alpha and TGF beta still substantially inhibited GH4 cell proliferation. We next compared the actions of TGF alpha and TGF beta on two other well characterized prolonged GH4 responses. TGF alpha and TGF beta each increased GH4 cell adhesion, but differed in their effects on PRL production. This indicates that TGF alpha and TGF beta activate different signaling pathways in GH4 cells. Activin-A acted like TGF beta by enhancing cell-substratum adhesion and inhibiting PRL production, consistent with an interaction at a common receptor site. Taken together these results identify biological functions for TGF alpha, TGF beta, and activin-A on PRL cells and open the possibility that they may represent the direct in vivo mediators of estrogen action to regulate the growth of PRL cells in the anterior pituitary gland.
 ...
PMID:Transforming growth factor-alpha and -beta are potent and effective inhibitors of GH4 pituitary tumor cell proliferation. 200 14


1 2 3 4 5 6 7 8 9 10 Next >>