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)

Max is a helix-loop-helix zipper protein that associates in vitro with Myc family proteins to form a sequence-specific DNA-binding complex. We show here, by means of a coimmunoprecipitation assay with anti-Myc and anti-Max antibodies, that Myc and Max are associated in vivo and essentially all of the newly synthesized Myc can be detected in a complex with Max. This complex possesses specific DNA-binding activity for CACGTG-containing oligonucleotides. Although Max itself is a highly stable protein, Myc is rapidly degraded during or after its association with Max. In vivo Max is shown to be a nuclear protein phosphorylated by casein kinase II, and alternatively spliced forms of Max are expressed in cells. Furthermore, the levels of Max expression are equivalent in quiescent, mitogen-stimulated, and cycling cells. We conclude that the highly regulated rate of Myc biosynthesis is likely to be a limiting step in the formation of Myc:Max complexes.
...
PMID:Myc and Max associate in vivo. 173 Apr 11

cDNA clones encoding the plasma membrane Ca2+ pump isoform PMCA1 were obtained from rabbit stomach smooth muscle. The PMCA1 gene has a 154 base exon which can be alternatively spliced. In splices containing 0, 87 or 114 bases of this exon, the mRNA downstream from this position encodes a protein containing the peptide sequence Lys-Arg-Asn-Ser-Ser (KRNSS), which can be phosphorylated by cyclic-nucleotide-sensitive protein kinase. However, in those splices containing 154 bases, the mRNA encodes a protein that does not contain this sequence. The cDNA clone obtained in this study did not contain the latter exon, and thus it coded for KRNSS. The presence of the various splices of PMCA1 was determined in stomach smooth muscle and other tissues by reverse transcription followed by a polymerase chain reaction. Percentage of transcripts encoding the potentially cyclic-nucleotide-sensitive isoform in various tissues were as follows: liver, 100%; stomach mucosa, 100%; heart, 100%; stomach smooth muscle, 86%; aorta, 83%; brain, 55%. Thus brain was the only tissue which expressed a very high proportion of the isoform of PMCA1 that is insensitive to cyclic-nucleotide-dependent protein kinases.
...
PMID:Expression of cyclic-nucleotide-sensitive and -insensitive isoforms of the plasma membrane Ca2+ pump in smooth muscle and other tissues. 183 Apr 73

The catalytic (C) subunit is the phosphorylating component of the cAMP-dependent protein kinase, a key element in a multitude of hormonally controlled cellular functions. The C-subunit, thought to be a solitary protein until several years ago, is now known to be a group of isoforms comprising as yet C alpha, C beta, and C gamma. We report here the isolation of a full-length cDNA clone coding for a hitherto undiscovered isoform of the bovine C-subunit. The end parts of the 5'-coding region and the 5'-noncoding region of this 3365-base pair clone are unique, whereas the rest of the coding region and the 3'-noncoding region are identical to those of isoform C beta. The clone has therefore been named C beta 2. The deduced amino acid sequence of C beta 2 has a length of 397 amino acid residues and a calculated molecular mass of 46.1 kDa, thus being some 6 kDa higher than that of any known C-subunit. In vitro translation of clone C beta 2 resulted in a single 46-kDa protein. The unique amino-terminal sequence of C beta 2 lacks the usual myristoylation site of C-subunits. It contains a stretch of hydrophobic residues (residues 7-19) and a stretch which may fold into an amphiphilic alpha-helix (residues 16-27) conceivably serving targeting functions. The existence of isoform C beta 2 is confirmed by: (i) the isolation of a second independent C beta 2 clone, (ii) the development of products of expected size and sequence upon amplification from total RNA of various bovine tissues with the polymerase chain reaction using C beta 2-specific primers, and (iii) Northern blots probed with a cDNA fragment containing exclusively C beta 2 sequence. C beta 2 mRNA has a size of 4.4 kilobases and is expressed in various bovine tissues, mainly in heart and brain. Both the size and tissue distribution are indistinguishable from those of C beta mRNA, thus explaining the failure of previous investigations to distinguish it from C beta 2. Southern blotting and polymerase chain reaction with genomic DNA indicate that intron sequence(s) exist at the C beta 2/C beta deviation site (bases 267/268). The deviation site is equivalent to the exon 1/exon 2 splice site of the mouse C-subunit. Since splice sites are highly conserved and since not a single mutation is found downstream of the deviation site, it is tempting to suppose that C beta 2 and C beta are coded by one gene which possesses two alternatively spliced exons 1.
...
PMID:Isoform C beta 2, an unusual form of the bovine catalytic subunit of cAMP-dependent protein kinase. 200 51

The amino acid sequences of two catalytic (C) subunits of Aplysia cAMP-dependent protein kinase (cAPK) have been deduced from the nucleotide sequences of cDNAs generated from neuronal poly(A)+ RNA. Both subunits contain 352 residues and are identical except for amino acids 142-183, which differ at 10 out of 42 positions. They derive from alternatively spliced transcripts of a single gene (CAPL) containing two mutually exclusive exon cassettes. CAPL transcripts are present in several classes of identified neurons containing transmitter-sensitive adenylate cyclase, including sensory cells, bag cells, and the left pleural giant cell. Combinatorial expression of the various regulatory (R) and C subunits might produce kinase isoforms with distinct roles in neuronal modulation. Alternatively, holoenzymes with overlapping properties together might contribute to the definition of individual cell types and physiological states.
...
PMID:Two catalytic subunits of cAMP-dependent protein kinase generated by alternative RNA splicing are expressed in Aplysia neurons. 248 6

The prototype mitogen-activated protein (MAP) kinase module is a three-kinase cascade consisting of the MAP kinase, extracellular signal-regulated protein kinase (ERK) 1 or ERK2, the MAP/ERK kinase (MEK) MEK1 or MEK2, and the MEK kinase, Raf-1 or B-Raf. This and other MAP kinase modules are thought to be critical signal transducers in major cellular events including proliferation, differentiation, and stress responses. To identify novel mammalian MAP kinase modules, polymerase chain reaction was used to isolate a new MEK family member, MEK5, from the rat. MEK5 is more closely related to MEK1 and MEK2 than to the other known mammalian MEKs, MKK3 and MKK4. MEK5 is thought to lie in an uncharacterized MAP kinase pathway, because MEK5 does not phosphorylate the ERK/MAP kinase family members ERK1, ERK2, ERK3, JNK/SAPK, or p38/HOG1, nor will Raf-1, c-Mos, or MEKK1 highly phosphorylate it. Alternative splicing results in a 50-kDa alpha and a 40-kDa beta isoform of MEK5. MEK5 beta is ubiquitously distributed and primarily cytosolic. MEK5 alpha is expressed most highly in liver and brain and is particulate. The 23 amino acids encoded by the 5' exon in the larger alpha isoform are similar to a sequence found in certain proteins believed to associate with the actin cytoskeleton; this alternatively spliced modular domain may lead to the differential subcellular localization of MEK5 alpha.
...
PMID:Isolation of MEK5 and differential expression of alternatively spliced forms. 749 18

We report here that osteoblasts and osteoblast-like osteosarcoma cells express PMCA1b, an alternatively spliced transcript of plasma membrane Ca(2+)-ATPase. Synthetic oligonucleotide pairs were designed based upon unique regions of the cDNA encoding known PMCA isoforms (PMCA1-3) and used as primers in PCR-mediated amplification of cDNA synthesized from ROS 17/2.8 osteosarcoma cell RNA. A product was observed only when PMCA1-specific primers were present; no products were seen with PMCA2 or PMCA3 primers unless cDNA synthesized from rat brain RNA was present. Examination of the cDNA encoding the C terminus of PMCA1 from ROS 17/2.8 cells revealed that the mRNA is spliced to yield the PMCA1b isoform, a Ca(2+)-ATPase containing a consensus phosphorylation site for cAMP-dependent protein kinase A and a modified calmodulin binding domain. PMCA1b was also detected in UMR-106-01 osteosarcoma cells and unpassaged primary rat calvarial osteoblasts. These results suggest that the regulation of osteoblast function by agents that act via cAMP-mediated pathways may involve alterations in the activity of the plasma membrane Ca(2+)-ATPase.
...
PMID:Osteoblasts express the PMCA1b isoform of the plasma membrane Ca(2+)-ATPase. 750 68

We have used cDNA probes derived from the secretory form of the Na-K-Cl cotransporter to screen both cortical and medullary rabbit kidney cDNA libraries. A sequence of 4750 bases was identified from multiple clones. The DNA encodes a protein containing 1099 amino acids, which is 61% identical over its length to the secretory Na-K-Cl cotransporter from shark rectal gland. From analysis of amino acid hydropathy, we predict that this putative renal Na-K-Cl cotransporter has 12 transmembrane helices and large N- and C-terminal cytoplasmic regions. Two sites for N-linked glycosylation are predicted on an extracellular loop. Three potential sites for modulation by protein kinase A are in the C-terminal cytoplasmic domain. Most of the isolated renal cDNA clones were identical over all regions of overlap; however, there was a 96-bp region for which there were three different but homologous variants (A, B, and F). This region of divergence was identified as an alternatively spliced cassette exon since clones were identified that contained intronic DNA as well as consensus splice acceptor sites that bounded the region. Tissue Northern blot analysis revealed a broad band at approximately 5.1 kb that was unique to the kidney. High-stringency Northern blot analysis of cortical and medullary mRNA using antisense oligonucleotides synthesized over each of the three cassette exons revealed that the isoforms were differentially distributed within the kidney--B almost exclusively in cortex, F almost exclusively in medulla, and A about equally distributed.
...
PMID:Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter are differentially distributed within the rabbit kidney. 751 6

In vitro selection technology has been used to purify RNA aptamers from a random sequence pool that can bind to, and specifically inhibit, protein kinase C beta II. Two of the selected RNA aptamers bind to this isozyme of protein kinase C with nanomolar affinities and inhibit activation with unprecedented selectivity; the highly related, alternatively spliced beta I isozyme, which differs by 23 residues, is inhibited with 1 order of magnitude lower potency; the next most similar isozyme, alpha, shows no detectable inhibition. The production of isozyme-specific inhibitors of protein kinase C opens the possibilities for dissecting the roles of specific protein kinase Cs in the myriad of intracellular signalling pathways.
...
PMID:Isozyme-specific inhibition of protein kinase C by RNA aptamers. 752 7

Glutamate-gated ion channels mediate most excitatory synaptic transmission in the mammalian central nervous system and play major roles in synaptic plasticity, neuronal development, and in some neuropathological conditions. Recent studies have suggested that protein phosphorylation of neuronal glutamate receptors by cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) may regulate their function and play a role in some forms of synaptic plasticity. To test whether these protein kinase effects are due to direct phosphorylation of the receptors and to further examine the sites and mechanisms by which the receptors are modulated, we transiently expressed recombinant glutamate receptors in HEK-293 cells and studied their biochemical and biophysical properties. Our results indicate that the kainate-preferring receptor GluR6 is phosphorylated by PKA, primarily on a single serine in the proposed major intracellular loop. Moreover, using the whole cell patch clamp recording technique, we have shown that phosphorylation at this site increases the amplitude of the GluR6-mediated glutamate current without significantly altering its dose-response, current-voltage relation or desensitization kinetics. In other experiments, we have demonstrated that the NMDA receptor subunit NR1 is phosphorylated by PKC on several distinct sites, and most of these sites are located within a single alternatively spliced exon in the C-terminal domain. These findings suggest that RNA splicing can regulate NMDA receptor phosphorylation and that, contrary to the previously proposed membrane topology model, the NR1 C-terminus is intracellular. Furthermore, in HEK-293 cells co-transfected with NR2A and NR1 subunits containing the C-terminal exon with the PKC phosphorylation sites, our preliminary studies indicate that the NMDA-evoked current is potentiated by intracellular PKC. We are currently examining PKC effects on the NMDA-evoked current responses of mutant NR1 receptors that lack the C-terminal phosphorylation sites. These studies provide evidence that glutamate receptors are directly phosphorylated and functionally modulated by protein kinases. Moreover, by identifying phosphorylation sites within the receptor proteins, our results provide information about the structure and membrane topology of these receptors.
...
PMID:Glutamate receptor modulation by protein phosphorylation. 753 May 47

In guinea pig ventricle, the protein kinase A-regulated Cl- current (ICl) is conducted by an alternatively spliced isoform of the cystic fibrosis transmembrane conductance regulator. We studied muscarinic regulation of this current using the whole-cell configuration of the patch-clamp technique. Acetylcholine (ACh) antagonized activation of ICl activated by 1 microM isoproterenol (ISO) in a concentration-dependent manner. The concentration of ACh that produced a half-maximal effect (K1/2) was 36 nM, the slope factor was 1.1, and the relative magnitude of the Cl- conductance at maximally effective concentrations of ACh (Gmin) was 21% of that observed in the presence of ISO alone. In the presence of 100 nM atropine, a competitive antagonist at the muscarinic receptor, the K1/2 value for ACh inhibition of ICl was increased to 4.3 microM, but the slope factor and Gmin were not affected, which indicated that the dissociation constant (KB) for atropine was < 1 nM. ACh-induced inhibition of the ISO-activated ICl was also blocked by the quaternary ammonium compound tetraethylammonium (TEA). Like atropine, TEA increased the K1/2 value for ACh inhibition of ICl without affecting the slope factor or Gmin. Schild analysis confirmed that TEA is also a competitive antagonist at the muscarinic receptor, with a KB value of 137 microM. However, tetramethylammonium (TMA), a structurally related compound, acted as an agonist at the muscarinic receptor. TMA inhibited ICl activated by 1 microM ISO with a K1/2 value of 342 microM, a slope factor of 0.87 and a Gmin value of 17%. Increasing the concentration of ISO shifted the K1/2 value for both ACh and TMA inhibition of ICl to higher concentrations and increased Gmin, without significantly affecting the slope factor. These results indicate that muscarinic regulation of ICl depends on the level of beta adrenergic stimulation in a functionally uncompetitive manner. They also suggest that TMA acts like ACh, a full agonist at the muscarinic receptor. Furthermore, we conclude that quaternary ammonium compounds, which are often used as ion substitutes and direct ion channel blockers, should be used with caution because of the significant and diverse effects they exert at muscarinic receptors.
...
PMID:Muscarinic regulation of the cardiac CFTR Cl- current by quaternary ammonium compounds. 753 45


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

---