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)

As detected by coimmunoprecipitation from PC12 cells, NGF induces rapid association between ERK1 (a growth factor-activated serine/threonine protein kinase) and gp140prototrk NGF receptors. In contrast, no such association is found with the closely related ERK2. Anti-trk immunocomplexes generated from NGF-treated cells also contain protein kinase activity that shares many properties with soluble ERK1. The association of both ERK1 protein and ERK-like kinase activity with gp140prototrk is maximal by 5 min of NGF treatment, persists for approximately 1 hr, and subsequently declines by 18 hr. Treatment with either basic fibroblast growth factor, epidermal growth factor, or orthovanadate also leads to association of ERK1 with gp140prototrk without tyrosine phosphorylation of the latter. The interaction between ERK1 and gp140prototrk may prove relevant to the NGF mechanism.
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PMID:NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk. 146 7

A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.
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PMID:Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei. 152 47

A homology probing approach was utilized to isolate a new human protein kinase. Deoxyoligonucleotide probes recognizing a conserved subdomain in the COOH-terminal portion of protein kinases identified a cDNA clone encoding a putative kinase with predicted serine/threonine phosphorylation specificity. The full-length, 1.7-kilobase pair cDNA hybridizes to 1.7- and 3.4-kilobase mRNA transcripts in a number of tissues. The size of the encoded protein is 454 amino acids and consists of an NH2-terminal 130-residue segment, which may represent a regulatory region, followed by a 324-residue catalytic domain. Comparisons and alignments of the primary sequence and predicted secondary structure of the catalytic region to other known kinases reveal that the new kinase, denoted "CLK" (for CDC-like kinase), represents a prototype for a new family of human protein kinases bearing significant homology to the yeast cdc2/CDC28 kinases that regulate the cell cycle.
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PMID:Molecular cloning of a novel human cdc2/CDC28-like protein kinase. 170 89

An antiserum raised against a delta-protein kinase C (delta-PKC)-specific peptide recognized the purified calcium-unresponsive 76-kDa protein kinase of porcine spleen in the native and the denatured form. This antiserum was used to demonstrate the delta-PKC-like enzyme in spleen of different species, in various cell types and in murine tissues by immunoblotting of the respective extracts. Due to species differences, delta-PKC-like kinases with slightly different molecular weights were observed. The enzyme was found to be present in primary murine keratinocytes, primary bovine endothelial cells, and many cell lines originating from human, rat, and murine tissues. It was present also in all murine tissues tested, predominantly in epidermis, uterus, placenta, lung, brain, spleen, and kidney. In contrast to the conventional alpha, beta, gamma-PKC, it was located almost exclusively in the particulate fraction. The delta-like PKC could be demonstrated in the epidermis and brain of newborn mice, and in both tissues its concentration increased dramatically between day 7 and 14 after birth. The delta-PKC-like kinase of mouse epidermis (p82-kinase) was down-regulated after topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin. The amount of the enzyme decreased to less than 20% of the controls within 16 h and recovered almost completely within 72 h after TPA. The existence of the delta-PKC-like kinase in mouse skin, papillomas, and carcinomas could also be demonstrated by immunocytochemical staining of the respective sections. The enzyme was observed predominantly in epithelial layers. A remarkable immunostaining of nuclei in skin sections disappeared after TPA treatment of the animals.
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PMID:Immunological demonstration of a calcium-unresponsive protein kinase C of the delta-type in different species and murine tissues. Predominance in epidermis. 186 Aug 75

Protein kinase C from human brain was isolated and characterized. A protein kinase M like kinase of molecular weight 63 kDa was also partially purified and identified by its immunological properties similar to those of kinase C. The kinase M like kinase activity, devoid of Ca2+ and phospholipids dependency, was also characterized by its inhibition profile by several ligands. Since this kinase phosphorylates a G protein (M.W. 36 kDa) and decreases its GTPase activity which could be restored by alkaline phosphatase, it is concluded that this kinase M like kinase could interact with G protein mediated events of neuronal responses.
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PMID:Isolation of human brain protein kinase C: evidence for kinase C catalytic fragment modulating G protein-GTPase activity. 189 69

Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and interleukin-6 (IL6) compose a family of distantly related cytokines that initiate signaling by inducing either homodimerization of the "beta" signal transducing receptor component gp130 (in the case of IL6) or heterodimerization between gp130 and the gp130-related LIFR beta (in the case of CNTF, LIF, and OSM); dimerization of beta receptor components in turn activates members of the Jak/Tyk family of receptor-associated tyrosine kinases. Here we report that CNTF, LIF, OSM, and IL6 induce most of the same protein tyrosine phosphorylations, regardless of the cell type assayed or whether they initiate signaling by inducing homo- or heterodimerization of beta components. Although several of the protein tyrosine phosphorylations induced by the CNTF/LIF/OSM/IL6 family of factors may correspond to novel tyrosine kinase targets, we have been able to demonstrate the involvement of known signaling molecules, such as phospholipase C gamma, phosphoinositol 3-kinase, phosphotyrosine phosphatase (PTP1D), pp120, SHC, GRB2, STAT91, Raf-1, and the mitogen-activated protein kinases ERK1 and ERK2, revealing substantial convergence not only between the pathways activated by this cytokine family and other cytokines, but with pathways previously known to be activated only by factors that utilize receptor tyrosine kinases. Our data suggest the beta receptor components can form complexes with some of the signaling proteins identified and may play some role in their recruitment.
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PMID:Ciliary neurotrophic factor/leukemia inhibitory factor/interleukin 6/oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors. 751 71

Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subunit that is derived from a 35-kDa brain- and neuron-specific protein called the neuronal Cdk5 activator (p35/p25nck5a) (Lew, J., Huang, Q.-Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H. (1994) Nature 371, 423-426; Tsai, L. H., Delalle, I., Caviness, V. S., Jr., Chae, T., and Harlow, E. (1994) Nature 371, 419-423). Upon screening of a human hippocampus library with a bovien Nck5a cDNA, we uncovered a distinct clone encoding a 39-kDa isoform of Nck5a. The isoform, designated the neuronal Cdk5 activator isoform (p39nck5ai), showed a high degree of sequence similarity to p35nck5a with 57% amino acid identity. Northern blot analysis detected its mRNA transcript in bovine and rat cerebrum and cerebellum, but not in any other rat tissues examined. In situ hybridization showed that Nck5ai was enriched in CA1 to CA3 of the hippocampus, but absent in the fimbria of hippocampal formation. Among seven cell lines in proliferating cultures, only PC12 and N2A, two cell lines capable of differentiating into neuron-like cells, were found to contain Nck5ai mRNA. A 30-kDa truncated form of Nck5ai expressed as a glutathione S-transferase fusion protein in Escherichia coli] was found to associate with Cdk5 to form an active Cdk5 kinase. Thus, the isoform shares many common characteristics with p35nck5a, including Ckd5 activating activity and brain- and neuron-specific expression. Both proteins show limited sequence homology to cyclins, suggesting that they define a new family of cyclin-dependent kinase-activating proteins.
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PMID:An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. 759 34

P13suc1 sepharose-conjugated beads were used to extract the kinases that phosphorylate neurofilaments in the squid giant axon. Using Western blots and in vitro kinase assays, we demonstrated the presence of an active cdc2-like kinase and its putative regulators such as cyclin E, p13, and p67 in axoplasm and a P13-axoplasm complex (P13-Ax). Protein kinase A (PKA) and casein kinase (CK) I and II were also found in the P13-Ax. Western blot analysis of the P13-Ax also demonstrated several axonal cytoskeletal components; e.g., neurofilaments (NFs; NF 60, 70, and 220), tubulin, actin, and microtubule-associated proteins. NF 220 and tubulin were phosphorylated by the kinases in the P13-Ax. To determine whether NFs bound directly to the P13 beads, or bound indirectly by association with cdc2 kinase, a washed, axon-derived neurofilament preparation that contained NFs, PKA, CKl, and tubulin, but no cdc2-like kinase, yielded no bound proteins after incubation with P13suc1. The wash supernatant from the neurofilament preparation, however, containing the cdc2-like kinase, did yield cytoskeletal components that bound to P13suc1. Moreover, a bacterial-expressed cdk5 associated with P13 beads was able to complex with selected cytoskeletal components in the washed neurofilament preparation. These data indicate that direct binding of P13 beads with a cdc2-like kinase could extract active multimeric complexes composed of axonal cytoskeletal proteins and kinases. Application of P13 chromatography may be useful in characterizing the network of functional interactions among cytoskeletal elements and protein kinases in neurons.
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PMID:P13suc1 associates with a cdc2-like kinase in a multimeric cytoskeletal complex in squid axoplasm. 766 4

Neurofilament (NF) protein [high molecular mass (NF-H)] is extensively phosphorylated in vivo. The phosphorylation occurs mainly in its characteristic KSP (Lys-Ser-Pro) repeat motifs. There are two major types of KSP motifs in the NF-H tail domain: KSPXKX and KSPXXX. Recent studies by two different laboratories have demonstrated the presence of a cdc2-like kinase [cyclin-dependent kinase-5 (cdk5)] in nervous tissue that selectively phosphorylates KSPXKX and XS/TXK motifs in NF-H and lysine-rich histone (H1). This article describes the identification of phosphatases dephosphorylating three different substrates: histone (H1), NF-H in a NF preparation, and a bacterially expressed C-terminal tail domain of NF-H, each containing KSPXKX repeats phosphorylated in vitro by cdk5. Among various phosphatases identified, protein phosphatase (PP) 2A from rabbit skeletal muscle appeared to be the most effective phosphatase in in vitro assays. Three phosphatase activity peaks--P1, P2, and P3--were partially purified from frozen rat spinal cord by ion exchange and size exclusion column chromatography and then characterized on the basis of biochemical, pharmacological, and immunochemical studies. One of the three peaks was identified as PP2A, whereas the others were mixtures of both PP2A and PP1. These three peaks could dephosphorylate cdk5-phosphorylated 32P-histone (H1), 32P-NF-H in the NF preparation, and 32P-NF-H tail fusion protein. These studies suggest the involvement of PP2A or a PP2A-like activity in the regulation of the phosphorylation state of KSPXKX motifs in NF-H.
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PMID:Neuronal cyclin-dependent kinase-5 phosphorylation sites in neurofilament protein (NF-H) are dephosphorylated by protein phosphatase 2A. 776 48

Neurofilament proteins and the neuron-specific microtubule-associated protein tau are phosphorylated in vivo at sites conforming to the phosphorylation consensus motif of the cell-cycle-control protein kinase, p34cdc2-cyclin. Abnormalities in the phosphorylation of these proteins are associated with neurodegenerative disorders, such as amylotrophic lateral sclerosis and Alzheimer's disease. A cdc2-like kinase composed of cyclin-dependent kinase 5 (cdk5) and a brain-specific regulatory subunit is proposed to be responsible for the cdc2-like phosphorylation of these neuronal proteins.
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PMID:Neuronal cdc2-like kinase. 787 42


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