Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myelin basic protein (MBP)-phosphorylating enzymes present during maturation and early embryogenesis of the sea star (Pisaster ochraceus) were investigated. The major maturation-activated MBP kinase (p45 Mapk) was molecularly cloned based on tryptic sequence information obtained with the purified enzyme and shown to be highly related to human Erk1 with 76% amino acid identity. Kinase assays and immunoblotting studies revealed that Mapk remained highly active until 12 h post-fertilization (PF), after which it declined. By 4 days PF, Mapk protein was no longer detectable. At 3 h PF, about half of the detectable MBP phosphotransferase activity could be attributed to a 75 kDa protein kinase that was distinct from Mapk. Like Mapk, this protein phosphorylated MBP mostly on threonine residues, but it failed to phosphorylate a peptide (APRTPGGRR) based upon the Thr-97 MAP kinase phosphorylation site in MBP. Rather, it phosphorylated a peptide (AAQKRPSQRTKYLA) patterned after the N-terminus of MBP. Our studies also showed a dramatic increase in MBP phosphotransferase activity occurred by 4 days PF that arose from a third kinase that phosphorylated MBP solely on serine residues. This kinase exhibited the following substrate substrate preference: AAQKRPSQRTKYLA, peptide substrate for S6 kinases (AKRRRLSSLRASTSKSESSQK) > MBP > histone H1 > prota-mine > casein > APRTPGGRR. This kinase was not appreciably affected by addition of phosphatidylserine/diacylglycerol, or the staurosporine analogue Roche Compound 3, but it was partly inhibited by a protein kinase C pseudosubstrate peptide. Gel filtration analysis revealed an apparent molecular mass of 41 kDa for the enzyme. Therefore, at least two novel MBP-phosphorylating enzymes distinct from Mapk are preferentially activated following fertilization and early embryogenesis of the sea star.
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PMID:Characterization of fertilization-modulated myelin basic protein kinases from sea star: regulation of Mapk. 1050

We previously demonstrated that lysophosphatidylcholine up-regulated endothelial nitric-oxide synthase promoter activity by increasing Sp1 binding via the action of protein serine/threonine phosphatase 2A (Cieslik, K., Zembowicz, A., Tang, J.-L., and Wu, K.K. (1998) J. Biol. Chem. 273, 14885-14890). To characterize the regulation of basal endothelial nitric-oxide synthase promoter activity and the signaling pathway through which lysophosphatidylcholine augments endothelial nitric-oxide synthase transcription, we used a casein kinase 2 inhibitor coupled with immunoprecipitation to demonstrate that basal Sp1 binding and endothelial nitric-oxide synthase promoter activity were controlled by casein kinase 2 complexed with protein serine/threonine phosphatase 2A. Casein kinase 2 catalyzed protein serine/threonine phosphatase 2A phosphorylation thereby inhibiting its activity. Lysophosphatidylcholine selectively activated p42/p44 mitogen-activated protein kinase. Purified extracellular regulated kinase 2 blocked casein kinase 2 activity and increased protein serine/threonine phosphatase 2A activity, resulting in an increased Sp1 binding and endothelial nitric-oxide synthase promoter activity. These results indicate that Sp1 binding to its cognate site on the endothelial nitric-oxide synthase promoter and its transactivation of endothelial nitric-oxide synthase is regulated by post-translational Sp1 phosphorylation and dephosphorylation through a dynamic interaction between casein kinase 2 and protein serine/threonine phosphatase 2A.
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PMID:Transcriptional regulation of endothelial nitric-oxide synthase by an interaction between casein kinase 2 and protein phosphatase 2A. 1057 32

In tobacco cells, osmotic stress induced the rapid activation of two protein kinases that phosphorylate myelin basic protein. Immunological studies demonstrated that the 48-kD kinase is the salicylic acid-induced protein kinase (SIPK), a member of the mitogen-activated protein kinase family. SIPK was activated 5 to 10 min after the cells were exposed to osmotic stresses, and its activity persisted for approximately 30 min. In contrast, the 42-kD kinase was activated within 1 min after osmotic stress, and its activity was maintained for approximately 2 hr. Moreover, in addition to myelin basic protein, the 42-kD kinase phosphorylated casein and two transcription factors, c-Jun and ATF-2. This latter enzyme was inactivated by a serine/threonine-specific phosphatase but, unlike SIPK, was not affected by a tyrosine-specific phosphatase. After the 42-kD kinase was purified to apparent homogeneity, tryptic peptide analysis indicated that it is a homolog of Arabidopsis serine/threonine kinase1 (ASK1).
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PMID:Osmotic stress induces rapid activation of a salicylic acid-induced protein kinase and a homolog of protein kinase ASK1 in tobacco cells. 1063 15

Casein kinase I (CKI) is a widely expressed protein kinase family implicated in diverse processes including membrane trafficking, DNA repair, and circadian rhythm. Despite the large number of CKI genes, few biologically relevant substrates have been identified. As an approach to better defining the spectrum of CKI substrates, we extended a recently described in vitro expression cloning (IVEC) strategy. Polypeptides pools were screened for kinase-dependent electrophoretic mobility shifts. Ten putative CKI substrates were isolated from an initial sample of 3000 random cDNA clones. Candidate substrates include proteins involved in RNA metabolism (a putative RNA helicase, the nucleolar protein hNOP56, and hnRNP A1, and ribosomal proteins L4, L8, and L13), as well as keratin 17, a necdin-related protein, and the calcium-binding proteins desmoglein 2 and annexin II. The same pools were also screened with active ERK2, and four substrates identified: aldolase, NSD-like protein, uracil-DNA glycosylase, and HHR23A. IVEC is an effective method to identify novel protein kinase substrates.
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PMID:Identification of casein kinase I substrates by in vitro expression cloning screening. 1067 43

Light induced rapid and transient activation of a 46-kDa protein kinase in soybean photomixotrophic cell culture. This kinase was designated as LAP kinase (light signal-activated protein kinase). Activation of LAP kinase in response to light was associated with tyrosine phosphorylation of the kinase, and treatment of the kinase with protein tyrosine phosphatase abolished its activity. The LAP kinase efficiently phosphorylated myelin basic protein and histone, but did not phosphorylate casein. Phospho-amino acid analysis indicated that the LAP kinase was a serine/threonine protein kinase. These results indicated that the LAP kinase is related to the MAP kinase family of protein kinases.
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PMID:Light activates a 46-kDa MAP kinase-like protein kinase in soybean cell culture. 1129 28

Acrolein, which is a highly reactive formaldehyde generated by lipid peroxidation, can affect skin and cause various disorders. The effect of exposure of human keratinocytes to acrolein on cell surface-oriented signal transduction into cells was examined. Incubation of human keratinocytes with a relatively low concentration (50 microM) of acrolein caused a prompt and selective induction of tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as a 180-kDa molecule during the period from 5-30 min after the start of incubation. This early event was followed by an increase in the density and number of phosphotyrosine-containing proteins during the period from 60-120 min after the start of incubation. The catalytic activity of EGFR as measured by the levels of autophorphorylation and phosphorylation of an exogenously added substrate, casein, in in vitro kinase assay, greatly increased as early as 1 min after the start of incubation and then decreased gradually 30 min later. MAP family kinases, including ERK, JNK, and p38 kinase, and the potentially downstream transcription factor c-Jun were all promoted for phosphorylation/activation during a period of 5-30 min. Selective prompt phosphorylation/activation of EGFR followed by phosphorylation of MAP family kinases and c-Jun and their blockade by a specific EGFR inhibitor, AG1478, suggested that activation of EGFR is the major, and possibly single, cell surface element for intracellular signal transduction in acrolein-treated cells. Incubation of human keratinocytes with 50 microM of acrolein induced atypical apoptosis with morphologic apoptotic features with low-grade oligonucleoside-sized DNA fragmentation. Partial inhibition of such a cytopathic effect of acrolein on human keratinocytes by preincubation with AG1478 suggests the involvement of an EGFR-mediated signal pathway for atypical apoptosis. These results provide new information on acrolein-induced cell surface-oriented signal transduction to human keratinocytes, and this information may be useful for understanding the pathogenesis of a number of skin diseases in response to environmental acrolein and acrolein-generating ultraviolet irradiation.
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PMID:Acrolein induces activation of the epidermal growth factor receptor of human keratinocytes for cell death. 1132 22

Wnt signals play important roles in development and oncogenesis and are transduced through at least two pathways: a canonical beta-catenin-dependent and a beta-catenin-independent cascade. Casein kinase I (CKI) is required in both invertebrates and vertebrates to transduce canonical Wnt signals. However, its role in the beta-catenin-independent pathway was unknown. During vertebrate embryogenesis, the beta-catenin-independent cascade is thought to control cell movements and has been postulated to be analogous to the Drosophila planar cell polarity pathway, which signals through the JNK cascade. Here, we report that blocking CKI function inhibits embryonic morphogenesis and activates JNK in cell lines. These studies suggest that CKI might also act in the beta-catenin-independent pathway and indicate a role for CKI during convergence extension in early vertebrate development.
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PMID:The casein kinase I family: roles in morphogenesis. 1143 44

RAGE (receptor for advanced glycation end products) is a multiligand cell surface molecule of the immunoglobulin superfamily. It was originally described as a receptor for protein adducts formed by glycoxidation (AGEs) that accumulate in diseases such as diabetes and renal failure. Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. Moreover, Caco-2 cells were incubated in the presence of AGEs. Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation.
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PMID:RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. 1170 25

Wnt signals control decisive steps in development and can induce the formation of tumors. Canonical Wnt signals control the formation of the embryonic axis, and are mediated by stabilization and interaction of beta-catenin with Lef/Tcf transcription factors. An alternative branch of the Wnt pathway uses JNK to establish planar cell polarity in Drosophila and gastrulation movements in vertebrates. We describe here the vertebrate protein Diversin that interacts with two components of the canonical Wnt pathway, Casein kinase Iepsilon (CKIepsilon) and Axin/Conductin. Diversin recruits CKIepsilon to the beta-catenin degradation complex that consists of Axin/Conductin and GSK3beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals. Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for axis formation, which depends on beta-catenin signaling. Diversin is also involved in JNK activation and gastrulation movements in zebrafish. Diversin is distantly related to Diego of Drosophila, which functions only in the pathway that controls planar cell polarity. Our data show that Diversin is an essential component of the Wnt-signaling pathway and acts as a molecular switch, which suppresses Wnt signals mediated by the canonical beta-catenin pathway and stimulates signaling via JNK.
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PMID:The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. 1218 62

We show here that the YIL113w gene of Saccharomyces cerevisiae encodes a functional protein phosphatase. Yil113p shows no activity in vitro towards either phosphorylated casein or myelin basic protein. However, Yil113p dephosphorylates activated extracellular signal-regulated kinase 2 MAP kinase indicating that it is a dual-specificity MAP kinase phosphatase. In support of this we find that Yil113p specifically interacts with the stress-activated Slt2/Mpk1p MAP kinase of S. cerevisiae. Furthermore, expression of Yil113p causes the dephosphorylation of Slt2/Mpk1p in vivo, while expression of an inactive mutant of Yil113p causes the accumulation of phosphorylated Slt2/Mpk1p. We conclude that the physiological target of YIL113p is Slt2/Mpk1p.
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PMID:YIL113w encodes a functional dual-specificity protein phosphatase which specifically interacts with and inactivates the Slt2/Mpk1p MAP kinase in S. cerevisiae. 1222 Jun 58


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