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

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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)

Atrial natriuretic peptide (ANP) binds to a transmembrane receptor having intrinsic guanylyl cyclase activity; this receptor has been designated GC-A. Binding of ANP to GC-A stimulates its catalytic activity, resulting in increased production of the second messenger, cyclic GMP. Here we show that GC-A can be expressed in insect cells using a recombinant baculovirus and that the expressed protein retained its abilities to bind ANP and to function as an ANP-activated guanylyl cyclase. In addition, GC-A produced in insect cells was absolutely dependent on the presence of adenine nucleotides for activation by ANP. Millimolar concentrations of ATP were required for optimal activation. The relative potencies of various nucleotides for activation was adenosine 5'-O-(thiotriphosphate) greater than ATP greater than ADP, adenosine 5'-(beta, gamma-imino)triphosphate greater than ADP beta S. AMP had no effect. These studies suggest that binding of an adenine nucleotide, most likely to the protein kinase-like domain of GC-A, is absolutely required for ANP activation. Regulation of guanylyl cyclase activation by adenine nucleotides represents a novel mechanism for the modulation of signal transduction, possibly analogous in some respects to the role of guanine nucleotides and G proteins in the regulation of adenylyl cyclase activity.
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PMID:Adenine nucleotides are required for activation of rat atrial natriuretic peptide receptor/guanylyl cyclase expressed in a baculovirus system. 167 58

The human trk oncogene (originally identified in a colon carcinoma) was activated by a genetic rearrangement which resulted in replacement of the extracellular ligand-binding domain of the proto-trk transmembrane receptor by non-muscle tropomyosin sequences. The product of the trk oncogene, a protein of 70 kDa (p70trk), possesses tyrosine-specific protein kinase activity, is autophosphorylated in vitro on tyrosine and is phosphorylated on serine, threonine and tyrosine residues in trk-transformed cells. By site-directed mutagenesis of trk oncogene cDNA, the codon for lysine (367) at the putative ATP-binding site was changed to that for methionine and the codons for tyrosines (503 and 504) at the putative autophosphorylation sites were changed to those for phenylalanine. Replacement of Lys-367 by methionine results in a biologically inactive, kinase-negative mutant. Phe-ala mutants of trk showed drastically reduced ability to induce morphologic transformation, anchorage-independent growth and tumorigenicity in mouse NIH3T3 cells and showed reduced in vitro tyrosine kinase activity when assayed by autophosphorylation and phosphorylation of histone as exogenous substrate. The present study indicates the role of these specific conserved residues in regulating the biochemical and biological properties of p70trk oncoprotein.
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PMID:Mutational analysis of conserved residues in the tyrosine kinase domain of the human trk oncogene. 183 50

In bacterial chemotaxis, transmembrane receptor proteins detect attractants and repellents in the medium and send intracellular signals that control motility. The cytoplasmic proteins that transduce information from the receptors to the flagellar motor have previously been purified and many of their enzymatic activities have been identified. Here we report the reconstitution of the complete signal transduction system from purified components. The protein kinase, CheA, plays a central role in both the initial excitation response to stimuli as well as subsequent events associated with adaptation. This kinase provides phosphoryl groups to two acceptor proteins, CheY, which interacts with the flagellar motor, and CheB, which demethylates the receptors. The purified aspartate receptor, Tar, reconstituted into phospholipid vesicles, acts in conjunction with an auxiliary protein, CheW, to stimulate the rate of kinase autophosphorylation greater than 10-fold. This stimulation is inhibited by aspartate. The activity of the kinase is increased by increased levels of receptor methylation. This effect provides a mechanism that explains how changes in receptor methylation mediate adaptive responses to attractant and repellant stimuli.
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PMID:Reconstitution of the bacterial chemotaxis signal transduction system from purified components. 185 55

The protein kinase family of enzymes mediates the responses of eukaryotic cells to both inter- and intracellular signals. These enzymes are either serine/threonine-specific or tyrosine-specific. Many of the latter are transmembrane receptors and are important in transduction of extracellular signals across the plasma membrane, whereas few examples of receptor serine kinases have been reported. We have now identified a complementary DNA clone from Zea mays (L.) encoding a putative serine/threonine-specific protein kinase structurally related to the receptor tyrosine kinases. This structural similarity is evidence for a previously undescribed class of transmembrane receptor in higher plants likely to be involved in signal reception and transduction. Furthermore, the catalytic domain of this protein kinase is linked through a transmembrane domain to an extracellular domain similar to that of glycoproteins encoded in the self-incompatibility locus of Brassica which are involved in the self-recognition system between pollen and stigma.
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PMID:Relationship of a putative receptor protein kinase from maize to the S-locus glycoproteins of Brassica. 216 28

The protein kinase domains of v-kit, the oncogene of the acute transforming feline retrovirus HZ4-FeSV (HZ4-feline sarcoma virus), CSF-1R (macrophage colony stimulating factor receptor) and PDGFR (platelet derived growth factor receptor) display extensive homology. Because of the close structural relationship of v-kit, CSF-1R and PDGFR we predicted that c-kit would encode a protein kinase transmembrane receptor (Besmer et al., 1986a; Yarden et al., 1986). We have now determined the primary structure of murine c-kit from a DNA clone isolated from a brain cDNA library. The nucleotide sequence of the c-kit cDNA predicts a 975 amino acid protein product with a calculated mol. wt of 109.001 kd. It contains an N-terminal signal peptide, a transmembrane domain (residues 519-543) and in the C-terminal half the v-kit homologous sequences (residues 558-925). c-kit therefore contains the features which are characteristic of a transmembrane receptor kinase. Comparison of c-kit, CSF-1R and PDGFR revealed a unique structural relationship of these receptor kinases suggesting a common evolutionary origin. The outer cellular domain of c-kit was shown to be related to the immunoglobulin superfamily. The sites of expression of c-kit in normal tissue predict a function in the brain and in hematopoietic cells. N-terminal sequences which include the extracellular domain and the transmembrane domain as well as 50 amino acids from the C-terminus of c-kit are deleted in v-kit. These structural alterations are likely determinants of the oncogenic activation of v-kit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. 245 20

Signal transduction in Escherichia coli involves the interaction of transmembrane receptor proteins such as the aspartate receptor, Tar, and the products of four chemotaxis genes, cheA, cheY, cheW, and cheZ. It was previously shown that the cheA gene product is an autophosphorylating protein kinase that transfers phosphate to CheY, whereas the cheZ gene product acts as a specific CheY phosphatase. Here we report that the system can be reconstituted in vitro and receptor function can be coupled to CheY phosphorylation. Coupling requires the presence of the CheW protein, the appropriate form of the receptor, and the CheA and CheY proteins. Under these conditions the accumulation of CheY-phosphate is enhanced approximately 300-fold. This rate enhancement is seen in reactions using wild-type and "tumble" mutant receptors but not "smooth" mutant receptors. The increased accumulation of phosphoprotein was inhibited by micromolar concentrations of aspartate, using wild-type, but not tumble, receptors. These results provide evidence that the signal transduction pathway in bacterial chemotaxis involves receptor-mediated alteration of the levels of phosphorylated proteins. They suggest that CheW acts as the coupling factor between receptor and phosphorylation. The results also support the suggestion that CheY-phosphate is the tumble signal.
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PMID:Transmembrane signal transduction in bacterial chemotaxis involves ligand-dependent activation of phosphate group transfer. 264 76

TRK is a human transforming gene generated in a colon carcinoma by a somatic rearrangement that fused a nonmuscle tropomyosin gene to sequences that shared extensive homology with members of the tyrosine-protein kinase supergene family. These sequences are likely to be derived from a transmembrane receptor gene whose putative ligand binding domain has been replaced by tropomyosin. In the present studies, we have expressed the entire coding sequences of the TRK oncogene as well as its protein kinase-related carboxyl-terminal domain in Escherichia coli. Antisera raised against these bacteria-synthesized TRK polypeptides has allowed us to identify the gene product of the TRK oncogene as a 70-kDa protein. Immunoprecipitates containing p70TRK have an associated protein kinase activity specific for tyrosine residues. Moreover, p70TRK is phosphorylated in vivo in serine (75%), threonine (20%), and tyrosine (5%) residues. Finally, immunofluorescence and cellular fractionation studies indicate that p70TRK is preferentially located in the cytoplasmic fraction.
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PMID:Identification and biochemical characterization of p70TRK, product of the human TRK oncogene. 347 1

CD30 is a transmembrane receptor of the nerve growth factor/tumor necrosis factor receptor superfamily. Its expression associated with Hodgkin's lymphoma and a subset of non-Hodgkin's lymphoma. Recently, its ligand (CD30L) has been cloned. CD30L enhances the proliferation of peripheral T cells and the Hodgkin's cell line HDLM-2 but seems to exert antiproliferative effects on large cell anaplastic lymphoma cell lines. Since tyrosine kinases are critical regulators of cell growth, we investigated whether CD30L induced changes in cellular tyrosine phosphorylation in CD30-positive lymphoma cell lines. Stimulation with CD30L or with an agonistic mAb against CD30, M44, induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of a cytosolic protein of M(r) 42,000 (p42) in the Hodgkin's lymphomas cell line HDLM-2 but not in other CD30-positive lymphomas. In HDLM-2 cells, the phrobol ester phorbol 12-myristate 13-acetate also stimulated tyrosine phosphorylation of p42, and this effect was enhanced by M44. In marked contrast, agents stimulating the protein kinase A pathway, like forskolin or dibutyryl cAMP, did not affect tyrosine phosphorylation of P42. By immunoprecipitation with mAbs against mitogen-activated protein kinase (MAPK; p42ERKII), a M(r) 42,000 protein was identified which comigrated with p42 on SDS gels and which was phosphorylated on tyrosine residues in response to stimulation of CD30. Immune complex kinase assays showed that M44 mAb induced the activation of MAPK (p42ERKII) and the phosphorylation of a MAPK substrate, myelin basic protein. Taken together, the results suggest that CD30L induces the tyrosine phosphorylation and activation of the MAPK p42ERKII isoform in HDLM-2 cells. These findings may have implications for the understanding of the pathogenesis of Hodgkin's disease.
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PMID:CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin's lymphoma cell line. 754 87

Within the Drosophila embryo, tube and the protein kinase pelle transduce an intracellular signal generated by the transmembrane receptor Toll. This signal directs import of the rel-related protein dorsal into ventral and ventrolateral nuclei, thereby establishing dorsoventral polarity. We show by immunolocalization that tube protein associates with the plasma membrane during interphase. We also find that tube sequences required for signaling interact with pelle in a yeast two-hybrid assay. We demonstrate that fusion of the pelle catalytic domain to the transmembrane receptor torso is sufficient to induce ventral fates; this activity is independent of Toll or tube. Lastly, we find that fusion of the tube protein to torso also induces ventral fates, but only in the presence of functional pelle. We propose a model wherein tube activates pelle by recruiting it to the plasma membrane, thereby propagating the axis-determining signal.
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PMID:Interaction of the pelle kinase with the membrane-associated protein tube is required for transduction of the dorsoventral signal in Drosophila embryos. 763 64

The development of erythroid progenitor cells depends upon exposure to the glycoprotein hormone, erythropoietin (EPO). Binding of EPO to its transmembrane receptor leads to the rapid tyrosine phosphorylation of several cellular targets including Shc, Raf-1, Gap120, the cloned EPO receptor (EPOR), pp100/97, and a M(r) 130,000 EPO-activated receptor-associated Janus protein tyrosine kinase, Jak2. A membrane-proximal cytosolic region of the EPOR recently has been shown to be essential for the activation of Jak2 and sufficient for EPO-induced mitogenesis. This cytosolic region includes 8-12 amino acid box 1 and box 2 subdomains, which are conserved in certain class I receptors as well as a more distal 10-40 amino acid subdomain (extended box 2 subdomain, ExBx2), which likewise is implicated in mitogenic signaling. Through the expression of EPOR carboxyl-terminal truncation mutants in FDC-P1 cells, we presently show that an EPOR form truncated within the ExBx2 domain efficiently activates Jak2, yet is deficient in mitogenesis. Efficient expression of this mutant receptor at the cell surface and its ability to activate Jak2 indicate that poor mitogenic activity does not result from aberrant transport or folding. Rather, failure of this mutant to support proliferation above nominal rates underlines an apparent role for the EPOR ExBx2 subdomain in the activation of a distinct primary mitogenic effector.
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PMID:The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells. 803 73


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