G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
cyclin-dependent kinase-like 2 (CDC2-related kinase)
G00000168 (Mus musculus)

Databases (7)

ENSG00000138769 (Ensembl human gene)
8999 (Entrez Gene)
499 (G2Cdb plasticity & disease)
CDKL2 (GeneCards)
603442 (OMIM)
Marker Symbol
HGNC:1782 (HGNC)
Protein Sequence
Q92772 (UniProt)

Synonyms (2)

  • P56

Literature (8)

Pubmed - other

  • Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck).

    Marracci GH, Marquardt WE, Strehlow A, McKeon GP, Gross J, Buck DC, Kozell LB and Bourdette DN

    Portland Veterans Affairs Medical Center, R&D-65, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA. marracci@ohsu.edu

    Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner. LA treatment of Con A stimulated PBMC specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by LA was excluded by using monoclonal antibodies targeting different domains of CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting that endocytosis was involved in its downmodulation. LA is in a unique category of compounds that induce CD4 downmodulation by various mechanisms (e.g., gangliosides). We hypothesized that LA might induce dissociation of p56(Lck) from CD4, thus leading to its downmodulation. Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and precipitation of CD4. This unique immunomodulatory effect of LA warrants further investigation.

    Funded by: NCCIH NIH HHS: P50 AT00066-01

    Biochemical and biophysical research communications 2006;344;3;963-71

  • Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation.

    Tao J, Van Esch H, Hagedorn-Greiwe M, Hoffmann K, Moser B, Raynaud M, Sperner J, Fryns JP, Schwinger E, Gécz J, Ropers HH and Kalscheuer VM

    Max-Planck-Institute for Molecular Genetics, Berlin, Germany.

    Recently, we showed that truncation of the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene caused mental retardation and severe neurological symptoms in two female patients. Here, we report that de novo missense mutations in CDKL5 are associated with a severe phenotype of early-onset infantile spasms and clinical features that overlap those of other neurodevelopmental disorders, such as Rett syndrome and Angelman syndrome. The mutations are located within the protein kinase domain and affect highly conserved amino acids; this strongly suggests that impaired CDKL5 catalytic activity plays an important role in the pathogenesis of this neurodevelopmental disorder. In view of the overlapping phenotypic spectrum of CDKL5 and MECP2 mutations, it is tempting to speculate that these two genes play a role in a common pathogenic process.

    American journal of human genetics 2004;75;6;1149-54

  • Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling.

    Sarkar SN, Peters KL, Elco CP, Sakamoto S, Pal S and Sen GC

    Department of Molecular Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

    Double-stranded RNA (dsRNA), a frequent byproduct of virus infection, is recognized by Toll-like receptor 3 (TLR3) to mediate innate immune response to virus infection. TLR3 signaling activates the transcription factor IRF-3 by its Ser/Thr phosphorylation, accompanied by its dimerization and nuclear translocation. It has been reported that the Ser/Thr kinase TBK-1 is essential for TLR3-mediated activation and phosphorylation of IRF-3. Here we report that dsRNA-activated phosphorylation of two specific tyrosine residues of TLR3 is essential for initiating two distinct signaling pathways. One involves activation of TBK-1 and the other recruits and activates PI3 kinase and the downstream kinase, Akt, leading to full phosphorylation and activation of IRF-3. When PI3 kinase is not recruited to TLR3 or its activity is blocked, IRF-3 is only partially phosphorylated and fails to bind the promoter of the target gene in dsRNA-treated cells. Thus, the PI3K-Akt pathway plays an essential role in TLR3-mediated gene induction.

    Funded by: NCI NIH HHS: CA62220, CA68782

    Nature structural & molecular biology 2004;11;11;1060-7

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Toward a complete human genome sequence.

    Sanger Center and Genome Sequencing Center

    Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK;

    We have begun a joint program as part of a coordinated international effort to determine a complete human genome sequence. Our strategy is to map large-insert bacterial clones and to sequence each clone by a random shotgun approach followed by directed finishing. As of September 1998, we have identified the map positions of bacterial clones covering approximately 860 Mb for sequencing and completed >98 Mb ( approximately 3.3%) of the human genome sequence. Our progress and sequencing data can be accessed via the World Wide Web (http://webace.sanger.ac.uk/HGP/ or http://genome.wustl.edu/gsc/).

    Genome research 1998;8;11;1097-108

  • Molecular cloning of the epidermal growth factor-stimulated protein kinase p56 KKIAMRE.

    Taglienti CA, Wysk M and Davis RJ

    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01605, USA.

    A 56 kDa protein kinase was molecularly cloned from human fetal brain. This protein kinase (p56 KKIAMRE) shares homology with p42 KKIALRE (Meyerson et al., 1992) and is related to the proline-directed protein kinase group of signal transducing enzymes. The p56 KKIAMRE and p42 KKIALRE protein kinases exhibit mutually exclusive expression in reproductive tissues; p56 KKIAMRE in testis and p42 KKIALRE in ovary. p56 KKIAMRE and p42 KKIALRE may therefore contribute to signal transduction within these highly differentiated tissues. p56 KKIAMRE and p42 KKIALRE are activated by treatment of cells with epidermal growth factor (EGF). Although p56 KKIAMRE and p42 KKIALRE contain the MAP kinase dual phosphorylation motif Thr-Xaa-Tyr (Thr-Asp-Tyr), phosphorylation on Thr and Tyr within this motif is not required for EGF-stimulated protein kinase activity.

    Funded by: NCI NIH HHS: CA58396, CA65861

    Oncogene 1996;13;12;2563-74

  • Identification of the major tyrosine kinase substrate in signaling complexes formed after engagement of Fc gamma receptors.

    Marcilla A, Rivero-Lezcano OM, Agarwal A and Robbins KC

    Laboratory of Cellular Development and Oncology, NIDR, National Institutes of Health, Bethesda, Maryland 20892-4330, USA.

    We have recently identified the protein product of the c-cbl proto-oncogene as an SH3 binding protein expressed in macrophages. To investigate the possibility that p120c-cbl is involved in signaling pathways initiated by cell surface receptors for IgG (Fc gamma R), lysates of HL60 cells were examined for tyrosine phosphorylation of p120c-cbl upon Fc gamma R engagement. Our findings demonstrate that p120c-cbl is tyrosine-phosphorylated upon Fc gamma R engagement and that this molecule represents the major tyrosine kinase substrate in this signaling pathway. Protein complexes containing p120c-cbl, p72syk, and p56lyn were observed either in resting or activated cells. In vitro studies showed that the direct association between p120c-cbl and p56lyn was mediated by the SH3 domain of p56lyn.

    The Journal of biological chemistry 1995;270;16;9115-20

Gene lists (2)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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