Genomes and Genes
Experts and Doctors on protein serine threonine kinases in Israel
Topic: protein serine threonine kinases
- Mayan H, Melnikov S, Novikov I, Holtzman E, Farfel Z. Familial hyperkalemia and hypertension: pathogenetic insights based on lithium clearance. J Clin Endocrinol Metab. 2009;94:3010-6 pubmed publisher..Familial hyperkalemia and hypertension (FHHt) is caused by mutations in WNK kinases. Its pathogenesis is not completely understood...
- Shtutman M, Hershko T, Maissel A, Fima E, Livneh E. PKCeta associates with cyclin E/Cdk2 complex in serum-starved MCF-7 and NIH-3T3 cells. Exp Cell Res. 2003;286:22-9 pubmed..Thus, our studies support an important link between PKC and cell cycle control. ..
- Polager S, Ginsberg D. E2F mediates sustained G2 arrest and down-regulation of Stathmin and AIM-1 expression in response to genotoxic stress. J Biol Chem. 2003;278:1443-9 pubmed..Thus, functional complexes containing E2F and RB family members appear to be essential for repressing expression of critical mitotic regulators and maintaining the G(2)/M checkpoint. ..
- Agmon Levin N, Gilburd B, Kivity S, Katz B, Flitman Katzevman I, Shoenfeld N, et al. Anti-ribosomal-P antibodies in lupus patients and healthy controls: evaluation of three ELISA assays. Isr Med Assoc J. 2009;11:403-6 pubmed
- Inbal B, Shani G, Cohen O, Kissil J, Kimchi A. Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Mol Cell Biol. 2000;20:1044-54 pubmed..Possible functional connections between DAP kinase and DRP-1 are discussed. ..
- Savitsky K, Sfez S, Tagle D, Ziv Y, Sartiel A, Collins F, et al. The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum Mol Genet. 1995;4:2025-32 pubmed..The complete sequence of the ATM gene product provides useful clues to the function of this protein, and furthers understanding of the pleiotropic nature of the A-T mutations. ..
- Zhang S, Kovalenko A, Cantarella G, Wallach D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity. 2000;12:301-11 pubmed..The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex. ..
- Peretti D, Dahan N, Shimoni E, Hirschberg K, Lev S. Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell. 2008;19:3871-84 pubmed publisher..We propose that Nir2, OSBP, and CERT function coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities. ..
- Kovalenko A, Chable Bessia C, Cantarella G, Israel A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature. 2003;424:801-5 pubmed..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology. ..
- Raveh T, Hovanessian A, Meurs E, Sonenberg N, Kimchi A. Double-stranded RNA-dependent protein kinase mediates c-Myc suppression induced by type I interferons. J Biol Chem. 1996;271:25479-84 pubmed..Taken together these results prove the existence of direct or indirect links between PKR and c-Myc suppression, thereby placing this gene along one of the complementary growth suppressive pathways that are triggered by interferons. ..
- Zhu X, Tang G, Galili G. The activity of the Arabidopsis bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase enzyme of lysine catabolism is regulated by functional interaction between its two enzyme domains. J Biol Chem. 2002;277:49655-61 pubmed
- Sessa G, Raz V, Savaldi S, Fluhr R. PK12, a plant dual-specificity protein kinase of the LAMMER family, is regulated by the hormone ethylene. Plant Cell. 1996;8:2223-34 pubmed publisher..The tissue in this zone is known to constitutively express ethylene-regulated genes...
- Litvak V, Shaul Y, Shulewitz M, Amarilio R, Carmon S, Lev S. Targeting of Nir2 to lipid droplets is regulated by a specific threonine residue within its PI-transfer domain. Curr Biol. 2002;12:1513-8 pubmed
- Jona G, Livi L, Gileadi O. Mutations in the RING domain of TFB3, a subunit of yeast transcription factor IIH, reveal a role in cell cycle progression. J Biol Chem. 2002;277:39409-16 pubmed..To conclude, in the present study we bring another demonstration of the multifunctional nature of TFIIH. ..
- Grozinsky Glasberg S, Rubinfeld H, Nordenberg Y, Gorshtein A, Praiss M, Kendler E, et al. The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. Mol Cell Endocrinol. 2010;315:87-94 pubmed publisher..RAD001 seems to have potent anti-proliferative effect in human MTC cells, which suggest that clinical trials of this agent are of considerable interest. ..
- Paz K, Liu Y, Shorer H, Hemi R, LeRoith D, Quan M, et al. Phosphorylation of insulin receptor substrate-1 (IRS-1) by protein kinase B positively regulates IRS-1 function. J Biol Chem. 1999;274:28816-22 pubmed..These findings implicate PKB as a positive regulator of IRS-1 functions. ..
- Erez O, Kahana C. Screening for modulators of spermine tolerance identifies Sky1, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis. Mol Cell Biol. 2001;21:175-84 pubmed..While deletion or overexpression of SKY1 did not significantly affect Pma1p activity, the ability of overexpressed Sky1p, Ptk1p, and Ptk2p to increase sensitivity to LiCl depends on the integrity of PPZ1 but not of ENA1. ..
- Dvash E, Kra Oz G, Ziv C, Carmeli S, Yarden O. The NDR kinase DBF-2 is involved in regulation of mitosis, conidial development, and glycogen metabolism in Neurospora crassa. Eukaryot Cell. 2010;9:502-13 pubmed publisher..We propose that DBF-2 functions as a link between Hippo and glycogen metabolism pathways. ..
- Opatowsky Y, Sasson Y, Shaked I, Ward Y, Chomsky Hecht O, Litvak Y, et al. Structure-function studies of the G-domain from human gem, a novel small G-protein. FEBS Lett. 2006;580:5959-64 pubmed..Our ensuing biochemical characterization indicates that Gem G-domain markedly prefers GDP over GTP. Two known functions of Gem are distinctly affected by spatially separated clusters of mutations. ..
- Mayan H, Munter G, Shaharabany M, Mouallem M, Pauzner R, Holtzman E, et al. Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation. J Clin Endocrinol Metab. 2004;89:4025-30 pubmed
- Kalo E, Buganim Y, Shapira K, Besserglick H, Goldfinger N, Weisz L, et al. Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II. Mol Cell Biol. 2007;27:8228-42 pubmed..These data provide important insights into the molecular mechanisms that underlie mutant p53 "gain of function" pertaining to the TGF-beta signaling pathway. ..
- Chaussepied M, Ginsberg D. Transcriptional regulation of AKT activation by E2F. Mol Cell. 2004;16:831-7 pubmed..AKT activation was shown to inhibit E2F1induced apoptosis. Therefore, our results suggest the existence of a negative feedback loop involving E2F and AKT. ..
- Kamer I, Sarig R, Zaltsman Y, Niv H, Oberkovitz G, Regev L, et al. Proapoptotic BID is an ATM effector in the DNA-damage response. Cell. 2005;122:593-603 pubmed..These results implicate BID as an ATM effector and raise the possibility that proapoptotic BID may also play a prosurvival role important for S phase arrest. ..
- Dagon Y, Avraham Y, Berry E. AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2alpha in adipocytes. Biochem Biophys Res Commun. 2006;340:43-7 pubmed..Thus, AMPK may diminish adiposity via reduction of fat cell number through eIF2alpha-dependent translation shutdown. ..
- Zanin Zhorov A, Tal G, Shivtiel S, Cohen M, Lapidot T, Nussbaum G, et al. Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and inflammation. J Immunol. 2005;175:276-85 pubmed..These effects of HSP60 could not be attributed to LPS or LPS-associated lipoprotein contamination. Thus, HSP60 can regulate T cell-mediated inflammation via specific signal transduction and SOCS3 activation. ..
- Sapir T, Sapoznik S, Levy T, Finkelshtein D, Shmueli A, Timm T, et al. Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration. J Neurosci. 2008;28:5710-20 pubmed publisher..Furthermore, the exact requirements for MARK2 and its kinase activity vary during the course of neuronal migration. Collectively, our results stress the requirements for the different roles of MARK2 during neuronal migration. ..
- Yao Z, Seger R. The ERK signaling cascade--views from different subcellular compartments. Biofactors. 2009;35:407-16 pubmed publisher..In this review, we discuss the intracellular localizations of different components of the ERK cascade, and the impact of these localizations on their activation and specificity. ..
- Sapir T, Shmueli A, Levy T, Timm T, Elbaum M, Mandelkow E, et al. Antagonistic effects of doublecortin and MARK2/Par-1 in the developing cerebral cortex. J Neurosci. 2008;28:13008-13 pubmed publisher..Our results stress the necessity for successful coupling between the polarity pathway and cytoplasmic dynein-dependent activities for proper neuronal migration. ..
- Ochaion A, Bar Yehuda S, Cohen S, Barer F, Patoka R, Amital H, et al. The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease. Cell Immunol. 2009;258:115-22 pubmed publisher..Taken together, NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation. ..
- Burgess H, Reiner O. Cleavage of doublecortin-like kinase by calpain releases an active kinase fragment from a microtubule anchorage domain. J Biol Chem. 2001;276:36397-403 pubmed..We propose that in neurons cleavage of DCLK by calpain represents a calcium responsive mechanism to regulate localization of the DCLK kinase domain. ..
- Sapir T, Cahana A, Seger R, Nekhai S, Reiner O. LIS1 is a microtubule-associated phosphoprotein. Eur J Biochem. 1999;265:181-8 pubmed..In vitro, LIS1 was phosphorylated by protein kinase CKII (casein kinase II), but not many other kinases that were tested. We suggest that LIS1 activity may be regulated by phosphorylation. ..
- Seger D, Gechtman Z, Shaltiel S. Phosphorylation of vitronectin by casein kinase II. Identification of the sites and their promotion of cell adhesion and spreading. J Biol Chem. 1998;273:24805-13 pubmed
- Malinin N, Boldin M, Kovalenko A, Wallach D. MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature. 1997;385:540-4 pubmed..It also blocked NF-kappaB induction by interleukin-1. Our findings indicate that NIK participates in an NF-kappaB-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor. ..
- Paas Y, Fishelson Z. Shedding of tyrosine and serine/threonine ecto-protein kinases from human leukemic cells. Arch Biochem Biophys. 1995;316:780-8 pubmed..Several endogenous proteins in the released membranes are phosphorylated by the ecto-PKs on serines and to a lesser extend on threonines. Two proteins (PTP79 and PTP54) are phosphorylated in a manganese-dependent manner on tyrosines. ..
- Koren I, Reem E, Kimchi A. DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol. 2010;20:1093-8 pubmed publisher..These results are consistent with a "Gas and Brake" model in which mTOR inhibition also controls a buffering mechanism that counterbalances the autophagic flux and prevents its overactivation under nutrient deprivation. ..
- Raveh Amit H, Maissel A, Poller J, Marom L, Elroy Stein O, Shapira M, et al. Translational control of protein kinase Ceta by two upstream open reading frames. Mol Cell Biol. 2009;29:6140-8 pubmed publisher..Our work further suggests that translational regulation could provide an additional level for controlling the expression of PKC family members, being more common than currently recognized. ..
- Aylon Y, Yabuta N, Besserglick H, Buganim Y, Rotter V, Nojima H, et al. Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic stress checkpoint and enables mutant H-Ras-driven cell transformation. Oncogene. 2009;28:4469-79 pubmed publisher..Our findings suggest that Lats2 might have an important role in quenching H-Ras-induced transformation, whereas silencing of Lats2 expression might serve as a mechanism to enable tumor progression. ..
- Levkovitz Y, Ben Shushan G, Hershkovitz A, Isaac R, Gil Ad I, Shvartsman D, et al. Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases. Mol Cell Neurosci. 2007;36:305-12 pubmed..These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance. ..
- Seger R, Krebs E. The MAPK signaling cascade. FASEB J. 1995;9:726-35 pubmed..In this review we emphasize primarily the first MAPK cascade to be discovered that uses the MEK and ERK isoforms and describe their involvement in different cellular processes. ..
- Aylon Y, Michael D, Shmueli A, Yabuta N, Nojima H, Oren M. A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization. Genes Dev. 2006;20:2687-700 pubmed..The Lats2-Mdm2-p53 axis thus constitutes a novel checkpoint pathway critical for the maintenance of proper chromosome number. ..
- Lubelsky Y, Reuven N, Shaul Y. Autorepression of rfx1 gene expression: functional conservation from yeast to humans in response to DNA replication arrest. Mol Cell Biol. 2005;25:10665-73 pubmed..We suggest that Rfx1 plays a role in the DNA damage response by down-regulating a subset of genes whose expression is increased in response to replication blocking and UV-induced DNA damage. ..
- Gilad S, Bar Shira A, Harnik R, Shkedy D, Ziv Y, Khosravi R, et al. Ataxia-telangiectasia: founder effect among north African Jews. Hum Mol Genet. 1996;5:2033-7 pubmed..This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community. ..
- Burgess H, Martinez S, Reiner O. KIAA0369, doublecortin-like kinase, is expressed during brain development. J Neurosci Res. 1999;58:567-75 pubmed
- Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci U S A. 1999;96:14973-7 pubmed..These findings suggest that in response to DNA strand breaks, ATM may promote p53 activity and stability by mediating simultaneous phosphorylation of both partners of the p53-MDM2 autoregulatory feedback loop. ..
- Shigaev A, Asher C, Latter H, Garty H, Reuveny E. Regulation of sgk by aldosterone and its effects on the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2000;278:F613-9 pubmed..A point mutation in the beta-subunit known to impair regulation of the channel by Nedd4 (Y618A) had no significant effect on the response to sgk...
- Burgess H, Reiner O. Alternative splice variants of doublecortin-like kinase are differentially expressed and have different kinase activities. J Biol Chem. 2002;277:17696-705 pubmed..Although this protein isoform was expressed mainly in the adult brain, the phosphorylated form was strongly enriched in embryonic brain and adult olfactory bulb, suggesting a possible role in migrating neurons. ..
- Erez O, Kahana C. Deletions of SKY1 or PTK2 in the Saccharomyces cerevisiae trk1Deltatrk2Delta mutant cells exert dual effect on ion homeostasis. Biochem Biophys Res Commun. 2002;295:1142-9 pubmed..A model that integrates these results to explain the mechanism of ion transport across the plasma membrane is proposed. ..
- Litvak V, Argov R, Dahan N, Ramachandran S, Amarilio R, Shainskaya A, et al. Mitotic phosphorylation of the peripheral Golgi protein Nir2 by Cdk1 provides a docking mechanism for Plk1 and affects cytokinesis completion. Mol Cell. 2004;14:319-30 pubmed..These results demonstrate a mechanism for coordinating mitotic and cytokinetic events with Golgi rearrangement during cell division. ..
- Ben Romano R, Rudich A, Tirosh A, Potashnik R, Sasaoka T, Riesenberg K, et al. Nelfinavir-induced insulin resistance is associated with impaired plasma membrane recruitment of the PI 3-kinase effectors Akt/PKB and PKC-zeta. Diabetologia. 2004;47:1107-17 pubmed..This defect manifests itself by impaired insulin-mediated recruitment of Akt/PKB and PKC-zeta to the plasma membrane. ..
- Cohen A, Grinblat B, Bessler H, Kristt D, Kremer A, Schwartz A, et al. Increased expression of the hPim-2 gene in human chronic lymphocytic leukemia and non-Hodgkin lymphoma. Leuk Lymphoma. 2004;45:951-5 pubmed..This relationship between hPim-2 and NHL and CLL raises a number of novel mechanistic options for the genesis and/or progression of some types of human lymphomas. ..
- Liu Y, Herschkovitz A, Boura Halfon S, Ronen D, Paz K, LeRoith D, et al. Serine phosphorylation proximal to its phosphotyrosine binding domain inhibits insulin receptor substrate 1 function and promotes insulin resistance. Mol Cell Biol. 2004;24:9668-81 pubmed
- Kontorovich T, Cohen Y, Nir U, Friedman E. Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and p53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers. Breast Cancer Res Treat. 2009;116:195-200 pubmed publisher..Germline promoter hypermethylation in the BRCA1 gene can be detected in about 5% of the female Israeli Jewish population, regardless of the BRCA1/2 status. The significance of this observation is yet to be determined. ..
- Eilam R, Peter Y, Groner Y, Segal M. Late degeneration of nigro-striatal neurons in ATM-/- mice. Neuroscience. 2003;121:83-98 pubmed..Thus, the Atm-/- mouse may model the extrapyramidal motor deficits seen in AT patients. ..
- Bank I, Koltakov A, Nir Glickman E, Goldstein I, Li J, Roitelman J, et al. Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen. Cell Immunol. 2003;223:35-45 pubmed..These results suggest new ways for functional modulation of activated T-cells interacting with collagen...
- Beery R, Haimsohn M, Wertheim N, Hemi R, Nir U, Karasik A, et al. Activation of the insulin-like growth factor 1 signaling pathway by the antiapoptotic agents aurintricarboxylic acid and evans blue. Endocrinology. 2001;142:3098-107 pubmed..Taken together, these results suggest that the survival/proliferation-promoting effects of ATA and EB in MCF-7 cells are transduced via the IGF-IR signaling pathway...
- Shani G, Henis Korenblit S, Jona G, Gileadi O, Eisenstein M, Ziv T, et al. Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. EMBO J. 2001;20:1099-113 pubmed..This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP-1, and a target for efficient activation of the kinase by various apoptotic stimuli. ..
- Laitman Y, Kaufman B, Lahad E, Papa M, Friedman E. Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast cancer. Isr Med Assoc J. 2007;9:791-6 pubmed..CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews. ..
- Gurevich M, Gritzman T, Orbach R, Tuller T, Feldman A, Achiron A. Laquinimod suppress antigen presentation in relapsing-remitting multiple sclerosis: in-vitro high-throughput gene expression study. J Neuroimmunol. 2010;221:87-94 pubmed publisher..These findings were demonstrated mainly via the NFkB pathway. Analysis of PBMC subpopulations identified activation of Th2 response in CD14+ and CD4+ cells and suppression of proliferation in CD8+ cells. ..
- Miguel S, Namdar Attar M, Noh T, Frenkel B, Bab I. ERK1/2-activated de novo Mapkapk2 synthesis is essential for osteogenic growth peptide mitogenic signaling in osteoblastic cells. J Biol Chem. 2005;280:37495-502 pubmed..These data define a novel mitogenic signaling pathway in osteoblasts whereby ERK1/2 stimulation of CREB phosphorylation and transcriptional activity as well as DNA synthesis are critically dependent on de novo Mapkapk2 synthesis. ..
- Porat Z, Erez O, Kahana C. Cellular localization and phosphorylation of Hrb1p is independent of Sky1p. Biochim Biophys Acta. 2006;1763:207-13 pubmed..Furthermore, we demonstrate that Hrb1p and additional putative Sky1p substrates, identified by computational approach, are not involved in mediating the spermine tolerant phenotype of sky1Delta cells. ..