Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors investigated the intracellular signal transduction for interleukin (IL)-1 beta-induced endothelin (ET) production by endothelial cells from cultured human umbilical vein (HUVEC). Cultured HUVEC released immunoreactive (iR)-ET into the media in a time-dependent manner and a significant increase of iR-ET production was observed by the addition of IL-1 beta. The stimulating effect of IL-1 beta on iR-ET production was respectively inhibited by protein kinase C (C kinase) inhibitor (H-7), Ca-calmodulin inhibitor (W-7), cyclic AMP-dependent protein kinase (A kinase) inhibitor (H-8) and tyrosine kinase inhibitor (genistain) in a dose-dependent fashion. The data suggested that intracellular signal transduction for IL-1 beta-induced iR-ET production were via such pathways as C kinase, A kinase, Ca-calmodulin and tyrosine kinase in combination or independently, though possible mediation by other pathways cannot be ruled out.
...
PMID:Intracellular signal transduction for interleukin-1 beta-induced endothelin production in human umbilical vein endothelial cells. 144 1

During the course of characterizing polymerase chain reaction products corresponding to protein kinases of a higher plant, Arabidopsis thaliana, we found a DNA fragment that potentially codes for a polypeptide with mosaic sequences of two classes of protein kinases, a tyrosine-specific and a serine/threonine-specific one. Overlapping complementary DNA (cDNA) clones coinciding with this fragment were isolated from an A. thaliana cDNA library. From their sequence analyses a protein kinase was predicted composed of 410 amino acid residues (APK1, Arabidopsis protein kinase 1), in which the kinase domain was flanked by short non-kinase domains. Upon expression of APK1 in Escherichia coli cells, several bacterial proteins became reactive with anti-phosphotyrosine antibody but not with the same antibody preincubated with phosphotyrosine, convincing us that APK1 phosphorylated tyrosine residues. APK1 purified from an over-producing E. coli strain showed serine/threonine kinase activity, and no tyrosine kinase activity, towards APK1 itself, casein, enolase, and myosin light chains. APK1 was thus concluded to be a novel type of protein kinase, which could phosphorylate tyrosine, serine, and threonine residues, though tyrosine phosphorylation seemed to occur only on limited substrates. Since the structure of the APK1 N-terminal portion was indicative of N-myristoylation, APK1 might associate with membranes and thereby contribute to signal transduction. The A. thaliana genome contained two APK1 genes close to each other (APK1a and APK1b).
...
PMID:Novel protein kinase of Arabidopsis thaliana (APK1) that phosphorylates tyrosine, serine and threonine. 145 Mar 80

A fungal metabolite, radicicol, with a macrocyclic ring induced the reversal of transformed phenotypes of v-src-transformed fibroblasts (Rous sarcoma virus-transformed 3Y1 rat fibroblast) at a quite low concentration of 0.1 microgram/ml. Actin stress fibers reappeared in the transformed cells after treatment with radicicol. Radicicol reduced the intracellular level of autophosphorylation of p60v-src as well as the level of other tyrosine-phosphorylated proteins in a dose-dependent manner. In vitro kinase assay revealed that radicicol effectively inhibited not only autophosphorylation but also transphosphorylation activities of purified p60v-src with a concentration producing 50% inhibition of 0.1 microgram/ml. However, radicicol showed no inhibitory effect on protein kinase C or protein kinase A. These results suggest that radicicol is a novel and specific protein-tyrosine kinase inhibitor and that the decreased level of tyrosine kinase activity of p60v-src causes reversion of transformed phenotypes of Rous sarcoma virus-transformed 3Y1 rat fibroblast. Furthermore, differentiation of Friend leukemia cells, which is one of the known characteristic phenomena associated with the inhibition of tyrosine kinase, was also induced in the concentration range of 0.05-0.5 microgram/ml, suggesting that the agent is useful for the analysis of differentiation as well as the kinase-mediated signal transduction.
...
PMID:Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. 145 81

Exposure of mammalian cells to DNA-damaging agents induces the ultraviolet (UV) response, involving transcription factor AP-1, composed of Jun and Fos proteins. We investigated the mechanism by which UV irradiation induces the c-jun gene. The earliest detectable step was activation of Src tyrosine kinases, followed by activation of Ha-Ras and Raf-1. The response to UV was blocked by tyrosine kinase inhibitors and dominant negative mutants of v-src, Ha-ras, and raf-1. This signaling cascade leads to increased phosphorylation of c-Jun on two serine residues that potentiate its activity. These results strongly suggest that the UV response is initiated at or near the plasma membrane rather than the nucleus. The response may be elicited by oxidative stress, because it is inhibited by elevation of intracellular glutathione. Using tyrosine kinase inhibitors, we demonstrate that the UV response has a protective function.
...
PMID:The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases. 147 46

1. The effect of a sunflower oil-enriched diet on plasma membrane-bound protein kinase C, protein kinase A, casein and tyrosine kinase activities was studied. 2. The diet induced an increase in the content of linoleic acid and a decrease in the content of palmitic acid. The anisotropy parameter (rs) of the fluorescence probe DPH and SDPH decreased strongly in the experimental group. 3. Protein kinase C was stimulated more than two times. Tyrosine kinase, protein kinase A and casein kinase activities were increased by 65, 57 and 40%, respectively. 4. We suggest that a more fluid lipid environment favours higher plasma membrane-bound protein kinase activities.
...
PMID:Effect of a sunflower oil-supplemented diet on protein kinase activities of rat liver plasma membranes. 147 8

Like many other cell surface receptors for nutrients and polypeptide hormones, the insulin receptor undergoes a complex endocytotic itinerary. Upon insulin binding, the receptor is activated as a tyrosine-specific protein kinase and autophosphorylates. This autophosphorylation is necessary for the receptor to internalize. After endocytosis, the ligand (insulin) and its receptor are dissociated. Most of the insulin is degraded, whereas the receptors are largely recycled to the cell surface. The signals in the receptor that control and specify its endocytotic pathway are beginning to be understood. Through the techniques of in vitro mutagenesis, noninternalizing receptors have been engineered and their structural and functional properties have been analyzed. For example, the immediate submembranous domain of the insulin receptor has been found to contain sequences (Gly-Pro-Leu-Tyr and, to a lesser extent, Asn-Pro-Gln-Tyr) that are necessary for normal endocytosis. Receptors deleted or mutated in these sequences retain tyrosine kinase activity but fail to undergo endocytosis. Unlike the better understood low density lipoprotein and transferrin receptors, however, these sequences are not sufficient for endocytosis. An insulin receptor with only these sequences exposed in the cytoplasm does not internalize. Tyrosine kinase activity is thought to be needed to lead to autophosphorylation and a conformational change that exposes the otherwise buried endocytosis sequences in the normally dimerized insulin receptor. Non-internalizing mutants of the insulin receptor have been used to examine the role of endocytosis in insulin action. It was found that an endocytosis-defective receptor could induce a short-term metabolic action of insulin (glycogen synthetase stimulation) as well as longer-term mitogenic effects of insulin. Furthermore, insulin action deactivated after the hormone was removed from the noninternalizing receptors. Apparently, endocytosis is not necessary for insulin action, but probably is important for removing the insulin from the cell so the target cell for insulin responds in a time-limited fashion to the hormone.
...
PMID:Mechanism and role of insulin receptor endocytosis. 147 59

Recent biochemical studies have suggested that apoptotic cell death is the molecular mechanism underlying the degeneration of ovarian follicles during atresia. Using a sensitive autoradiographic method for the detection of DNA fragmentation, we studied apoptosis in ovarian granulosa cells or intact follicles placed in serum-free culture as model systems to elucidate the hormonal regulation of atresia. Immature rats (25 days old) were primed for 2 days with 10 IU equine CG to induce a homogeneous population of mature preovulatory follicles. Granulosa cells isolated from these follicles contained predominantly intact high mol wt DNA. However, a time-dependent, spontaneous onset of internucleosomal DNA fragmentation characteristic of apoptotic cell death occurred in granulosa cells during culture. Treatment of granulosa cells with epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), or basic fibroblast growth factor (bFGF) inhibited the spontaneous onset of apoptotic DNA cleavage found during culture by 40-60%. In contrast, insulin-like growth factor I, insulin, TGF beta and tumor necrosis factor-alpha were ineffective. Likewise, activation of the protein kinase A or C pathways with forskolin or phorbol 12-myristate 13-acetate, respectively, did not prevent the onset of DNA fragmentation, although inclusion of a tyrosine kinase inhibitor (genistein) completely blocked the ability of EGF, TGF alpha, and bFGF to suppress apoptosis in granulosa cells. Similar to cultured granulosa cells, a spontaneous onset of apoptosis was also observed to occur in isolated preovulatory follicles during culture. Furthermore, treatment of follicles with EGF or bFGF inhibited the spontaneous initiation of apoptosis, and the suppressive effects of these growth factors were also attenuated by co-treatment with genistein.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Epidermal growth factor and basic fibroblast growth factor suppress the spontaneous onset of apoptosis in cultured rat ovarian granulosa cells and follicles by a tyrosine kinase-dependent mechanism. 148 Jan 80

The small GTP-binding protein Ras appears to be required for transformation and differentiation induced by tyrosine kinases. The Ras requirement may be limited to a few tyrosine kinase-regulated signaling pathways or may be universal for all tyrosine kinase actions. Because both Ras and the microtubule-associated protein 2 kinases ERK1 and ERK2 have been implicated in events that lead to neurite outgrowth, we explored the possibility that Ras and ERKs may lie on the same signaling pathway. Utilizing PC-12 rat adrenal pheochromocytoma cell lines that contain a dominant inhibitory Ras mutant (S17N-Ras(H)), we found that Ras was required for stimulation of the ERK cascade by nerve growth factor but apparently not by the heterotrimeric G protein activator AlF4-. Within this cascade, Ras appears to be upstream of an ERK activator, raising the intriguing possibility that Ras may directly regulate a serine/threonine protein kinase.
...
PMID:Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade. 149 81

The IL-2 receptor complex is minimally composed of two genetically unrelated subunits of relative molecular masses 55 and 75 kDa respectively. Structural information deduced from the cDNA sequences of either subunit have not revealed significant information as to the basis of the mechanisms of IL-2 receptor signal transduction. Nevertheless, IL-2 stimulates the activation of one or more tyrosine kinases requiring the functional participation of the p75 member of the receptor complex. Here we have developed the methods to isolate the receptor complex with an associated tyrosine protein kinase. Extracts of membrane glycoproteins from activated normal human T lymphocytes and cell lines demonstrated catalytic activation of tyrosine kinase activity when stimulated with IL-2. Purification of the receptor complex with biotinylated IL-2 revealed the presence of two dominant phosphotyrosyl-proteins of approximate molecular masses 58 and 97 kDa. Denaturation gel electrophoresis followed by renaturation of proteins associated with the IL-2 receptor complex demonstrated that the 97 kDa protein had catalytic autophosphorylation activity. The results indicate that the 58 and 97 kDa phosphotyrosyl-proteins can be found to co-precipitate with the IL-2 receptor complex and that the 97 kDa protein was demonstrated to have protein kinase activity. The association of such kinases with receptors devoid of catalytic structure may represent a unique paradigm of growth-factor receptor mechanisms.
...
PMID:Characterization of a tyrosine kinase activity associated with the high-affinity interleukin 2 receptor complex. 149 23

In conclusion, a multigene family (ERK) encoding protein kinases that have the capacity to convert tyrosine kinase signals to serine/threonine phosphorylation signals has been identified in animal and yeast cells. Protein kinases from this family have been shown to be phosphorylated on tyrosine and threonine in response to mitogens, as well as to have the capacity to autophosphorylate on these amino acid residues. In contrast, they apparently phosphorylate exogenous substrates on serine and/or threonine. Studies with cultured cells, Xenopus, and sea star oocytes have furthered our understanding of possible functions of Erks in vivo. These enzymes respond immediately to extracellular signals and are involved in G0-G1 transition (cultured cells), as well as in the M phase of oocyte maturation (Xenopus and sea star oocytes). Their usage of MAPs as substrates in vivo suggests a possible role of Erks in microtubule reorganization. ERK-encoded protein kinases use c-Jun, EGF receptor, and Raf-1 as potential substrates and can also reactivate dephosphorylated S6 kinase in vitro. Taken together, these data suggest that these enzymes play an important role in relaying the mitogenic signal by phosphorylating down-stream kinases and specific transcriptional factors, as well as having possible feedback function in the process of signal transduction. The results from the study of the yeast enzymes are pertinent to Erk activation in cells with nonmitogenic responses described above. In such cases, Erk protein kinases may act directly or indirectly on cyclins to arrest division and permit differentiation. The pathways influenced by ERK-like gene products in animal and yeast cells suggest that, depending on the downstream targets of substrates, transcriptional changes in a particular cell may occur to drive the cell cycle or, alternatively, withdrawal from the cell cycle may lead to specific differentiation events.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Erks: their fifteen minutes has arrived. 150 18


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

---