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 neural cell-adhesion molecule (N-CAM) is detected as at least 3 related polypeptides generated by alternative splicing of a single gene. In vivo the 2 larger polypeptides are phosphorylated, but the smallest polypeptide, which lacks a cytoplasmic domain, is not. We have found that the 2 larger polypeptides are phosphorylated in vivo on several common phosphorylation sites. Furthermore, the largest polypeptide has additional sites, suggesting that some phosphorylation occurs in that portion of the intracellular region unique to it. In vitro N-CAM is not a substrate for cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase, calcium/calmodulin-dependent protein kinase I, II, or III, protein kinase C, or casein kinase II. However, we have isolated 2 protein kinases from mammalian and avian brain that phosphorylate rodent and chicken N-CAM. On the basis of their chromatographic behavior and substrate specificity, the 2 kinases are glycogen synthase kinase 3 (GSK-3) and casein kinase I (CK I). The 2 kinases phosphorylate N-CAM rapidly, to a high stoichiometry and with a low Km for N-CAM, suggesting that the phosphorylation of N-CAM by these kinases is physiologically relevant. Both enzymes phosphorylate the 2 larger N-CAM polypeptides in vitro in the cytoplasmic domain on threonyl residues that are phosphorylated to a low level in vivo. In addition, the threonyl residues are close to seryl residues phosphorylated to a high level in vivo. Prior phosphorylation at the in vivo sites appears to be a prerequisite for phosphorylation by GSK-3 and CK I. Taken together, the results suggest that N-CAM may be physiologically phosphorylated on 2 sets of interrelated sites, one demonstrable in vivo and one in vitro. Phosphorylation on the "in vivo" sites is resistant to dephosphorylation and may be constitutive, while phosphorylation on the "in vitro" sites is much more labile.
...
PMID:Identification of two protein kinases that phosphorylate the neural cell-adhesion molecule, N-CAM. 254 81

Purified inhibitor of the cyclic AMP-dependent protein kinase (PKI) has been used as a probe to determine if hormone and cyclic AMP-induced activation of the cardiac alkaline triacylglycerol (TG) lipase is mediated through the cAMP-dependent protein kinase. Addition of CAM (cyclic AMP, Mg-ATP, and 3-isobutyl, 1-methylxanthine) to any of the four fractions (homogenate, 10,000 g supernatant, 105,000 g supernatant, or heparin-Sepharose eluate) from heparin perfused heart activated the TG lipase 60% to 110%. Preincubation of these fractions with 33 ng of PKI had no effect on control enzyme activity. Addition of PKI (33 ng) to extracts following CAM activation had little effect on homogenate TG lipase activity, but reduced activities in 10,000 g and 105,000 g supernatant fractions to their respective control levels, and inhibited TG hydrolase activity of activated heparin-Sepharose eluate to 50% below the control activity. If extracts were preincubated with PKI prior to CAM addition, TG lipase activity was reduced to approximately 50% below control levels in all fractions. PKI addition (33 ng) to 105,000 g supernatant obtained from hearts stimulated 60% by epinephrine perfusion reduced activity to 50% below the control level. PKI inhibition of TG lipase activity of 105,000 g supernatant could be reversed by adding 0.5 microgram of catalytic subunit of protein kinase (PKC) to the extract. The inhibition below control levels caused by CAM and PKI indicate that the PKI-PKC complex by itself or in combination with other extract molecules, has an inhibitory effect on the TG lipase.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Protein kinase inhibitor blocks the activation of a myocardial triacylglycerol lipase. 282 94

The crystal structure of the CAP dimer with cAMP has provided many insights into the action of this gene regulatory protein. The CAP subunit is divided into two domains that are connected by a hinge region. The carboxy-terminal domains bind to DNA and show both sequence and structural homologies with many other gene regulatory proteins from bacteria and viruses. The amino-terminal domain forms a binding site for cAMP and has been used to model the cAMP-binding domains of the regulatory subunits of mammalian cAMP-dependent protein kinase.
...
PMID:Crystallizing catabolite gene activator protein with cAMP for structural analysis. 284 95

The phenobarbital-inducible form of cytochrome P-450 purified from rabbit liver microsomes is phosphorylated by cAMP-dependent protein kinase at a single site, the serine residue in position 128 of the amino acid sequence. The serine is located in a characteristic recognition sequence for cAMP-dependent protein kinase and is part of a primary structure which is conserved during evolution, present also in phenobarbital-inducible rat cytochrome and cytochrome P-450 CAM from Pseudomonas putida. The contribution of these findings to our understanding of the structure and membrane topology of cytochrome P-450 LM2 and its turnover regulated by phosphorylation is discussed.
...
PMID:The site of cyclic AMP-dependent protein kinase catalyzed phosphorylation of cytochrome P-450 LM2. 299 Oct 8

The effect of CAM [cyclic AMP, Mg-ATP, and 3-isobutyl, 1-methylxanthine (MIX)] on triacylglycerol (TG) lipase activity in extracts from heparin-perfused rat heart was determined. TG lipase activity in homogenate, 10,000g supernatant, 105,000g supernatant, ammonium sulfate supernatant, and the eluate from heparin-Sepharose was increased between 62 and 151% when incubated with a combination of 0.3 mM cyclic AMP, 5 mM MgCl2, and 2 mM ATP. The addition of Mg-ATP + cyclic AMP caused a greater activation of TG lipase in the various fractions than did Mg-ATP + MIX or cyclic AMP + MIX. These results suggest that activation may be mediated by the classical cyclic AMP-protein kinase cascade. Control and CAM-stimulated activities were increased by heparin and inhibited by NaCl and protamine sulfate. In the absence of serum in the assay, the CAM system caused a relatively greater stimulation of lipolytic activity in each fraction compared to when serum was present in the assay. However, the absolute values were 6.1 to 16.3-fold greater with serum in the assay than without serum. In a similar manner, TG lipase activity was stimulated by CAM between 1.75 and 4.26-fold at pH 7.4, and only between 1.62 and 2.51-fold at pH 8.1. However, the absolute values at pH 8.1 were 6.77 to 31.83-fold greater than those seen at pH 7.4. These data demonstrate, for the first time, the cyclic AMP activation of a TG lipase above basal levels in cell-free fractions of rat heart. It is intriguing to speculate that the intracellular fraction of lipoprotein lipase may play a role in the hormonal regulation of cardiac TG lipolysis.
...
PMID:Cyclic AMP activation of a triglyceride lipase in broken cell preparations of rat heart. 301 40

The endogenous phosphorylation of serotonin binding protein (SBP), a soluble protein found in central and peripheral serotonergic neurons, inhibits the binding of 5-hydroxytryptamine (5-HT, serotonin). A protein kinase activity that copurifies with SBP (SBP-kinase) was partially characterized and compared with calcium/calmodulin-dependent protein kinase II (CAM-PK II). SBP itself is not the enzyme since heating destroyed the protein kinase activity without affecting the capacity of the protein to bind [3H]5-HT. SBP-kinase and CAM-PK II kinase shared the following characteristics: (1) size of the subunits; (2) autophosphorylation in a Ca2+-dependent manner; and (3) affinity for Ca2+. In addition, both forms of protein kinase phosphorylated microtubule-associated proteins well and did not phosphorylate myosin, phosphorylase b, and casein. Phorbol esters or diacylglycerol had no effect on either of the protein kinases. However, substantial differences between SBP-kinase and CAM-PK II were observed: (1) CAM enhanced CAM-PK II activity, but had no effect on SBP-kinase; (2) synapsin I was an excellent substrate for CAM-PK II, but not for SBP-kinase; (3) 5-HT inhibited both the autophosphorylation of SBP-kinase and the phosphorylation of SBP, but had no effect on CAM-PK II. These data indicate that SBP-kinase is different from CAM-PK II. Phosphopeptide maps of SBP and SBP-kinase generated by digestion with S. aureus V8 protease are consistent with the conclusion that these proteins are distinct molecular entities. It is suggested that phosphorylation of SBP may regulate the transport of 5-HT within neurons.
...
PMID:A Ca2+-dependent protein kinase activity associated with serotonin binding protein. 304 Sep 4

Protein kinases represent a diverse family of enzymes that play critical roles in regulation. The simplest and best-understood biochemically is the catalytic (C) subunit of cAMP-dependent protein kinase, which can serve as a framework for the entire family. The amino-terminal portion of the C subunit constitutes a nucleotide binding site based on affinity labeling, labeling of lysines, and a conserved triad of glycines. The region beyond this nucleotide fold also contains essential residues. Modification of Asp 184 with a hydrophobic carbodiimide leads to inactivation, and this residue may function as a general base in catalysis. Despite the diversity of the kinase family, all share a homologous catalytic core, and the residues essential for nucleotide binding or catalysis in the C subunit are invariant in every protein kinase. Affinity labeling and intersubunit cross-linking have localized a portion of the peptide binding site, and this region is variable in the kinase family. The crystal structure of the C subunit also is being solved. The C subunit is maintained in its inactive state by forming a holoenzyme complex with an inhibitory regulatory (R) subunit. This R subunit has a well-defined domain structure that includes two tandem cAMP binding domains at the carboxy-terminus, each of which is homologous to the catabolite gene activator protein in Escherichia coli. Affinity labeling with 8N3 cAMP has identified residues that are in close proximity to the cAMP binding sites and is consistent with models of the cAMP binding sites based on the coordinates of the CAP crystal structure. An expression vector was constructed for the RI subunit and several mutations have been introduced. These mutations address 1) the major site of photoaffinity labeling, 2) a conserved arginine in the cAMP binding site, and 3) the consequences of deleting the entire second cAMP binding domain.
...
PMID:CAMP-dependent protein kinase: prototype for a family of enzymes. 329 77

The Ca2+-dependent binding of [125I]calmodulin (CaM) to hepatic proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was utilized to identify CaM binding or "acceptor" proteins or CAPs. Two proteins of apparent molecular weight of 60,000 (CAP-60) and 45,000 (CAP-45) comprised greater than 80% of the Ca2+-dependent CaM binding in rat liver cytosol. CAP-60 and CAP-45 were partially purified by a variety of chromatographic steps, including affinity chromatography on CaM Sepharose. CAP-60 possessed a native molecular size of 400,000, indicating it to be the CaM-binding "subunit" of a larger oligomeric complex. In contrast, CAP-45 was monomeric as judged by gel filtration. Neither CAP-60 nor CAP-45 possessed chromatographic properties consistent with known CaM-dependent enzymes reported in the literature. Two-dimensional peptide mapping provided convincing evidence that CAP-60 and CAP-45 were unrelated to other well-characterized CAPs, namely Ca2+ (CaM)-dependent protein kinase II, calcineurin, or the CaM-dependent cyclic nucleotide phosphodiesterase. The relative abundance and high affinity for CaM could suggest that these novel target proteins, CAP-60 and CAP-45, represent a dominant pathway for CaM action in the mammalian liver.
...
PMID:Identification of high-affinity calmodulin-binding proteins in rat liver. 346 18

The rat alpha- and bovine alpha s1-casein genes have been isolated and their 5' sequences determined. The rat alpha-, beta-, gamma- and bovine alpha s1-casein genes contain similar 5' exon arrangements in which the 5' noncoding, signal peptide and casein kinase phosphorylation sequences are each encoded by separate exons. These findings support the hypothesis that during evolution, the family of casein genes arose by a process involving exon recruitment followed by intragenic and intergenic duplication of a primordial gene. Several highly conserved regions in the first 200 base pairs of the 5' flanking DNA have been identified. Additional sequence homology extending up to 550 base pairs upstream of the CAP site has been found between the rat alpha- and bovine alpha s1-casein sequences. Unexpectedly, the 5' flanking promoter regions are conserved to a greater extent than both the entire mature coding and intron regions of these genes. These conserved 5' flanking sequences may contain potential cis regulatory elements which are responsible for the coordinate expression of the functionally-related casein genes during mammary gland development.
...
PMID:Evolution of the casein multigene family: conserved sequences in the 5' flanking and exon regions. 395

Neural tubes isolated from quail embryos prior to epitheliomesenchymal transformation (EMT) and neural crest (NC) cell migration, when explanted onto fibronectin surfaces, replicated properties of normal NC morphogenesis such as (i) cell outgrowth, (ii) loss of A-CAM (N-cadherin) junctions and adoption of mesenchymal form, and (iii) development of HNK-1 immunoreactivity. The timetable of property (i) was essentially normal but the outgrowing cells were initially mainly epithelial, unlike NC outgrowth in vivo and in cultures of older neural tubes. Mesenchymal properties (ii) and (iii) were progressively and variably retarded relative to the in vivo timetable. Achievement of these properties by EMT was principally related to proximity to the neural tube and to preexisting mesenchymal cells, rather than being related temporally to the outgrowth timetable. This EMT, combined with a higher mitotic rate in the mesenchyme cells, resulted in the outgrowth passing from mainly epithelial at 16 hr to mainly mesenchymal at 48 hr in vitro. Immediate precocious EMT and outgrowth of A-CAM negative mesenchymal cells from pre-EMT neural tubes was stimulated by the protein kinase inhibitors staurosporine and bisindolymaleimide in a cycloheximide-independent manner. EMT could be induced not only on the dorsal (i.e., NC) side, but also on the ventral side of the neural tube, but the ventral cells were less sensitive than the dorsal cells, and with developmental age became still less sensitive while the dorsal cells became more sensitive. The results suggest that the complex events of EMT in the NC system are not obligatorily coregulated, can be triggered by epigenetic events involving differential protein phosphorylation, and may be controlled via intraneural signaling.
...
PMID:Control of epitheliomesenchymal transformation. I. Events in the onset of neural crest cell migration are separable and inducible by protein kinase inhibitors. 754 78


<< Previous 1 2 3 4 5 6 Next >>

---