Disease relevance of CDKL1

• The results indicate that in CNS, the KKIALRE protein is mainly a glial protein that is up-regulated in gliosis and that it probably plays no role in the hyperphosphorylation of tau in AD brains [1].
• Cultured astrocytes, neuroblastoma cells, and mouse brains contained the fetal form of KKIALRE protein [1].
• RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation [2].
• Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets [3].
• Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44(mapk) activation, and were blocked by the A(2a) purinoceptor antagonist ZM-241385 [4].

Psychiatry related information on CDKL1

• Neurons in normal brains and brains with Alzheimer's disease (AD) displayed no KKIALRE immunoreactivity [1].
• In response to the immobilization stress of rats, a useful model of emotional stress, rapid activation of p44/p42 mitogen-activated protein kinase was observed in the heart, followed by a transient upregulation of immediate early genes in the smooth muscle cells of coronary arteries, the endothelial cells and the myocardium [5].

High impact information on CDKL1

• Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation [6].
• Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade [7].
• Our results suggest that upregulation of caveolin-1 may be important in mediating contact inhibition and negatively regulating the activation state of the p42/44 MAP kinase cascade [7].
• NIH 3T3 cells harboring antisense caveolin-1 exhibit anchorage-independent growth, form tumors in immunodeficient mice and show hyperactivation of the p42/44 MAP kinase cascade [7].
• The longer-form p48 localizes in both the cytoplasm and the nucleus and suppresses apoptosis, whereas the shorter-form p42 predominantly resides in the cytoplasm and promotes cell differentiation [8].

Chemical compound and disease context of CDKL1

• A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coli BL21(DE3) strain [9].
• Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK) [10].
• The de-acylated product of PA, lysophosphatidic acid (LPA), which binds to members of the endothelial differentiation gene (EDG) family of receptors also stimulated p42/p44 MAPK in a pertussis toxin sensitive manner, but with an approximately 100 - 1000 fold lower potency compared with the different molecular species of PA [11].
• N(6)-cyclopentyladenosine-mediated increases in p42/p44 MAPK and p38 MAPK phosphorylation were blocked by the selective adenosine A(1) receptor antagonist 1,3-dipropylcyclopentylxanthine and following pretreatment of cells with pertussis toxin [12].
• These data suggest that sustained elevation of p42/44 MAPK activity may be required for the co-expression of alphavbeta6 integrin, which in turn may regulate the malignant potential of ovarian cancer cells via proteolytic mechanisms [13].

Biological context of CDKL1

• Overexpression of p48 provokes cell proliferation, which is inhibited by p42 [8].
• Thus, Ebp1 might regulate cell survival and differentiation through two distinctive p48 and p42 isoforms [8].
• Differentiation induction and proliferation inhibition were required for optimal suppression of leukemogenesis, as indicated by the effects of p42 C/EBPalpha, which were more potent than those of K298E C/EBPalpha, a mutant defective in DNA binding and transcription activation that failed to induce granulocyte differentiation [14].
• Overexpression of myc-tagged AUF1 p37 and p42 isoforms as well as suppression of endogenous AUF1 by RNA interference stabilized interleukin-6 mRNA [15].
• A S/M DNA replication checkpoint prevents nuclear and cytoplasmic events of cell division including centrosomal axis alignment and inhibits activation of cyclin-dependent kinase-like proteins in fucoid zygotes [16].

Anatomical context of CDKL1

• The KKIALRE immunoreactivity was detected primarily in fibrous astrocytes in white matter and perivascular and subpial spaces, as well as in Bergmann glia in the cerebellum [1].
• KKIALRE immunoreactivity was similar in neurons with and without neurofibrillary tangles [1].
• The biochemical properties and distribution of a Cdc2-related kinase, KKIALRE, were studied in brain tissues and cultured cells with antibodies to a subregion of KKIALRE protein deduced from cDNA [1].
• Moreover, nerve growth factor elicits extensive sprouting in p42 stably transfected PC12 cells, whereas p48 cells reveal modest neurite outgrowth [8].
• Here, we show that Ebp1 possesses two different isoforms, p48 and p42, which differentially mediate PC12 cell survival and differentiation [8].

Associations of CDKL1 with chemical compounds

• 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 [17].
• This S/M checkpoint also prevents tyrosine dephosphorylation of cyclin-dependent kinase-like proteins at the onset of mitosis [16].
• Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase [18].
• We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage [19].
• We examined the possibility that the alpha6A and alpha6B cytoplasmic domain variants of the alpha6beta1 integrin differentially activate p42 and p44 mitogen-activated protein (MAP) kinases [20].

Analytical, diagnostic and therapeutic context of CDKL1

• Enzymic determinations, Western blotting, and Northern hybridization were used to analyze expression of HGL mRNA, protein, lipase activity, and the p42/p44(mapk) activation status [21].
• Adhesion to laminin-1 mediated by the alpha6Abeta1 integrin triggered activation of a substantial fraction of total p42 and p44 MAP kinases as assessed using a mobility shift assay, immunoblot analysis with a phosphospecific MAP kinase antibody, and an immune complex kinase assay [20].
• The phosphorylation of eNOS and p42/p44(MAPK) was examined by immunocytochemistry [22].
• Hypothermia-induced loss of endothelial barrier function is restored after dopamine pretreatment: role of p42/p44 activation [23].
• Only in dopamine treated Lewis renal allografts subjected to cold storage, activation of p42/p44 occurred upon rewarming [23].

References