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

We report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[32P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO4/PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca2+/calmodulin, Ca2+/phospholipid, or EGTA. Similarities with the beta-adrenergic receptor protein kinase are discussed.
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PMID:An unusual protein kinase phosphorylates the chemotactic receptor of Dictyostelium discoideum. 283 47

Microtubules purified from brain tissue contain endogenous cyclic AMP (cAMP)-dependent protein kinase activity, and microtubule-associated protein 2 (MAP2) is the major substrate. Beef brain microtubules were prepared and used as a model system to study the differential effects of rationally selected cyclic nucleotide analogues on microtubule receptor protein kinase. Data are presented to indicate that the following molecular interactions are essential for activation of the phosphorylation of MAP2: (a) hydrogen bond formation toward the 2', 3', or 5' position, (b) interaction with phosphorus, and (c) no hydrogen bonds but hydrophobic interactions at the base moiety. Thus, the activation mechanism of the type II protein kinase associated with brain microtubules resembles the mechanism found in protein kinases of other systems. In addition, we have studied the effect of the two diastereomers of adenosine 3',5'-monophosphorothioate (cAMPS). The (Sp)-cAMPS isomer was found to activate MAP2 protein kinase, whereas the (Rp)-cAMPS isomer had no activating effect. In contrast, this compound was able to inhibit cAMP-stimulated MAP2 phosphorylation and thus acts as an antagonist of the Sp diastereomer and cAMP. Hence, this analogue provides a useful means to clarify further the effect of cAMP-dependent phosphorylation on functional properties in microtubules in general.
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PMID:In vitro phosphorylation of microtubule-associated protein 2: differential effects of cyclic AMP analogues. 299 22

Epidermal growth factor (EGF) receptor protein kinase activity, estimated by the use of peptide substrates, was reduced by as much as 70% after the treatment of intact A431 human carcinoma cells with EGF. The apparent decrease in protein kinase activity was observed after immunoprecipitation of the receptor or after purification of the receptor by lectin chromatography. By the use of [35S]methionine, it was determined that the total amount of receptor obtained was the same whether or not cells were treated with EGF. EGF stimulated the purified receptor protein kinase activity in vitro; however, the EGF-stimulated activity of receptor from EGF-treated cells continued to be reduced by as much at 70% compared to the EGF-stimulated activity from untreated cells. The reduction in receptor protein kinase activity induced by EGF may represent a feedback mechanism by which responsiveness to the growth factor is regulated.
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PMID:Suppression of protein tyrosine kinase activity of the epidermal growth factor receptor by epidermal growth factor. 301 45

The insulin-binding activity and insulin-dependent tyrosine protein kinase activity of the insulin receptor have been purified 2000-fold to homogeneity from human placental membranes. The purified receptor has one high-affinity binding site for insulin per mol of receptor. Its Vmax for phosphorylating angiotensin is 80 nmol of phosphate per min per mg of protein at 23 degrees C. The procedure used to purify the receptor includes chromatography on wheat germ agglutinin-agarose and on insulin-Sepharose. The purified receptor was eluted from insulin-Sepharose with 0.5 M NaCl and 1 mM dithiothreitol at pH 5.5. The addition of dithiothreitol was essential for recovery of the protein kinase. A silver-stained gel of the reduced purified receptor showed two major bands, Mr 95,000 (beta subunit) and Mr 135,000 (alpha subunit). The component of Mr 95,000 comigrated with the autophosphorylated beta subunit of the receptor. The latter was phosphorylated exclusively on tyrosine residues by an intramolecular process. In the presence of insulin, approximately 2 mol of phosphate was incorporated per mol of beta subunit. Two major beta subunit tryptic phosphopeptides were resolved by high-pressure liquid chromatography after autophosphorylation of the purified receptor in the presence or absence of insulin. It is concluded that the insulin binding and the insulin-dependent protein kinase are intrinsic components of the same oligomer since (i) they copurify to homogeneity, (ii) the purified receptor protein kinase is immunoprecipitated by polyclonal and monoclonal antibodies to the human insulin receptor, and (iii) phosphorylation of the beta subunit of the receptor occurs by an intramolecular reaction.
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PMID:Insulin receptor is an insulin-dependent tyrosine protein kinase: copurification of insulin-binding activity and protein kinase activity to homogeneity from human placenta. 620 18

Preparations of insulin receptor from cultured 3T3-L1 adipocytes and human placenta previously was found to catalyze the phosphorylation of the 90,000-dalton component of the insulin receptor on tyrosine residues. This insulin-dependent phosphorylation has now been shown to coincide with the generation of an activated, insulin-independent, receptor protein kinase. Activation is dependent upon ATP, divalent cations (Mg2+ and Mn2+), and insulin (half-maximal activation occurs at 6-8 nM insulin). The time required for activation is consistent with that needed for insulin-dependent self-phosphorylation of the receptor present in eluates from wheat germ lectin-agarose columns and in preparations of affinity-purified placental receptor. Activation proceeds unabated in the presence of soybean trypsin inhibitor at 0.1 mg/ml and the activated, insulin-independent, protein kinase sediments in 5-20% sucrose gradients at the same position as the unmodified receptor. Under steady-state conditions, the phosphorylated receptor binds insulin in the same fashion as the unmodified receptor. It is proposed that the self-phosphorylated form of the receptor is the insulin-activated protein kinase that catalyzes the phosphorylation of exogenous protein and peptide substrates. A corollary of this hypothesis is that enzymatic dephosphorylation may be essential for reversibly terminating the activity of the insulin-receptor protein kinase.
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PMID:Phosphorylation activates the insulin receptor tyrosine protein kinase. 657 82

Protein kinase-related domains of unknown function are present in the JAK family of protein tyrosine kinases and in receptor/guanylyl cyclases. I used the yeast two-hybrid system to screen for proteins interacting with the kinase-like domain of the atrial natriuretic peptide (ANP) receptor/guanylyl cyclase. A yeast strain was constructed expressing a fusion of this kinase-like domain to the lexA DNA-binding domain and containing a HIS3 gene under the control of lexA upstream activating sequences. These yeast cells were transformed with a plasmid library of mouse embryo cDNA fragments fused to the VP16 transcriptional activation domain. Cells containing VP16-fusion proteins interacting with the lexA-kinase-like domain fusion protein were selected by growth in the absence of histidine. A partial-length cDNA clone isolated by using this approach encoded a protein that interacted specifically with the ANP-receptor protein kinase-like domain both in yeast cells and in vitro. Tissue-specific expression of a 2.2-kb mRNA hybridizing to this cDNA paralleled the known pattern of ANP-receptor mRNA expression. A full-length cDNA clone isolated from a rat lung library was predicted to encode a 55-kDa protein containing at its amino terminus a targeting domain that binds to the ANP-receptor kinase-like domain and containing at its carboxyl terminus a putative protein-serine phosphatase domain. This protein is a possible candidate for the phosphatase involved in desensitizing the ANP receptor. Targeting of regulatory proteins may be an important function of protein kinase-like domains.
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PMID:Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor. 797 12

We have isolated two novel protein kinase genes, MHK and NAK, from the plant Arabidopsis thaliana by using low stringency hybridization with the catalytic domain of a putative plant receptor protein kinase. Sequence analysis of the cDNAs reveals that MHK is a member of the cdc2+ family of protein kinases and is particularly similar to the mak gene of rats; mak encodes a protein kinase that may play a role in spermatogenesis. NAK encodes a candidate protein kinase that is similar to the oncogenes met and abl. The homology that these two Arabidopsis genes share with other protein kinases suggests that they may play a role in the regulation of plant growth and development.
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PMID:Molecular cloning of two novel protein kinase genes from Arabidopsis thaliana. 821 20

The isolation of a maize cDNA clone that encodes a membrane spanning protein kinase related to the self-incompatibility glycoproteins (SLG) of Brassica and structurally similar to the growth factor receptor tyrosine kinases has recently been reported. Three distinct receptor-like protein kinase (RLK) cDNA clones from Arabidopsis thaliana have now been identified. Two of the Arabidopsis RLK genes encode SLG-related protein kinases but have different patterns of expression: one is expressed predominantly in rosettes while the other is expressed primarily in roots. The third RLK gene contains an extracellular domain that consists of 21 leucine-rich repeats that are analogous to the leucine-rich repeats found in proteins from humans, flies and yeast. The Arabidopsis leucine-rich gene is expressed at equivalent levels in roots and rosettes. These results show that there are several genes in higher plants that encode members of the receptor protein kinase superfamily. The structural diversity and differential expression of these genes suggest that each plays a distinct and possibly important role in cellular signaling in plants.
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PMID:Receptor-like protein kinase genes of Arabidopsis thaliana. 822 Apr 53

ARK1 is a vegetatively expressed receptor protein kinase gene isolated from Arabidopsis thaliana based on its sequence similarity to Brassica genes involved in pollen-stigma signaling and the self-incompatibility response. This paper shows that the kinase domain of ARK1 autophosphorylates on serine and threonine residues when expressed as a recombinant fusion protein. ARK1 produces a 2.9 kb transcript encoding a transmembrane receptor protein kinase and a 1.4 kb transcript encoding the receptor domain alone. Constitutive high-level expression of ARK1 transcripts in transgenic Arabidopsis resulted in severe stunting and also disrupted normal cellular expansion and differentiation.
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PMID:An S-locus-related gene in Arabidopsis encodes a functional kinase and produces two classes of transcripts. 881 66

Throughout development of the vertebrate retina, progenitor cells are multipotential, producing a variety of distinctive cell types. Little is known of the molecular mechanisms directing the determination of cell fate. We have examined retinal progenitor cells for expression of receptor tyrosine kinases in an attempt to define receptors that could allow a progenitor to respond to its environment. We found that the receptor tyrosine kinase Flk-1, previously shown to be expressed in endothelial cells, is also expressed in neural progenitor cells of the mouse retina. Flk-1 RNA expression in the retinal progenitors commences with the onset of neuronal differentiation and persists throughout retinal neurogenesis. Flk-1 RNA and protein levels in the retina vary temporally during development, as shown by in situ hybridization and Western blot analysis. Patterns of beta-galactosidase expression in mice containing the lacZ gene in place of the Flk-1 gene are consistent with Flk-1 being expressed in retinal progenitors. In addition, we show that the ligand of Flk-1, vascular endothelial growth factor (VEGF), is expressed in the developing retina by differentiated cells and that a chimeric ligand of VEGF fused to alkaline phosphatase binds to proliferating retinal progenitors. Furthermore, the neural retina-derived Flk-1 protein kinase is activated by VEGF in vitro. Thus, the Flk-1 receptor protein kinase is expressed on the surface of neural progenitors in mouse retina and may play a critical role in neurogenesis as well as in vasculogenesis.
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PMID:Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells. 881 91


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