Disease relevance of CHKA

• RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38-0.94) [1].
• These results indicate that CHK might participate in signaling in breast cancer cells by associating, via its SH2 domain, with ErbB-2 following heregulin stimulation [2].
• Immunostaining of the CHK protein in breast tissues demonstrated that primary invasive ductal carcinomas, stage II (13 of 15 cases) and stage I (8 of 15 cases), expressed the CHK protein, while this protein was not detected in the adjacent normal tissues from the same patients [2].
• Transformation of U937D cells with retrovirus vectors that contain the 3' untranslated region (3' UTR) of CK-B messenger RNA exhibited CK activity with no change in abundance of CK-B mRNA [3].
• The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves [4].

Psychiatry related information on CHKA

• In recent years, the roles of CK in cell growth and cell stress/defense mechanisms have been intensely investigated [5].
• Our findings identify p57Kip2 as a functionally relevant target recruited by bHLH transcription factors to induce cell cycle arrest in developing neuroblasts and suggest that deregulated expression of Id proteins may be an epigenetic mechanism to silence expression of this CKI in neural tumors [6].
• Recent advances in diverse fields, including developmental biology and chronobiology, have elucidated roles for CKI in regulating critical processes such as Wnt signaling, circadian rhythm, nuclear import, and Alzheimer's disease progression [7].
• In a time study we compared the analytical and clinical performance of the Tandem Icon QSR CK-MB enzyme-immunoassay (Hybritech) (creatine kinase-MB) and a creatine kinase-MB immunoinhibition method (Boehringer Mannheim GmbH) (creatine kinase-B) [8].

High impact information on CHKA

• A subline of U937 cells (U937D) was obtained in which creatine kinase B (CK-B) messenger RNA was present and bound to ribosomes, but CK activity was undetectable [3].
• Thus, a single, CKI-dependent phosphorylation event serves as a molecular switch for the Wnt pathway [9].
• These data suggest that phosphorylation of FADD by CKI is a crucial event during mitosis [10].
• Myristoylated, alanine-rich C-kinase substrate (MARCKS) is a lipopolysaccharide-induced protein kinase C (PKC) substrate that has been proposed to regulate actin-membrane interactions, as well as actin structure at the membrane [11].
• Warm retrograde and cold retrograde patients had sampling of the ascending aorta (antegrade) and the coronary sinus (retrograde) measuring pH, A-VO2 differences, and CK enzyme leak [12].

Chemical compound and disease context of CHKA

• CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population [1].
• Regulation of androgen-dependent prostatic cancer cell growth: androgen regulation of CDK2, CDK4, and CKI p16 genes [13].
• Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Putative effect of C kinase on alpha s-GTP-catalytic subunit interaction [14].
• Previous studies linked cAMP-mediated growth arrest in breast tumor cells to increased levels of cyclin kinase inhibitor (CKI), p21 [15].
• This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer [16].

Biological context of CHKA

• Choline kinase (CK) catalyzes the first phosphorylation reaction in the CDP-choline pathway for the biosynthesis of phosphatidylcholine (PC), yielding phosphocholine (P-Cho) from choline and ATP in the presence of Mg(2+) [5].
• These functions of CK do not seem to be directly related to the net PC biosynthesis but predict another important role of this enzyme in certain cell physiology [5].
• Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109 [1].
• Cyclin-dependent kinase inhibitors (CKI) have been identified as key effectors of cell cycle arrest in differentiating cells [6].
• Small hairpin RNAs directed against CKI revealed that the CKIalpha isoform contributed significantly to the inhibition of TRAIL-induced apoptosis [17].

Anatomical context of CHKA

• Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes [18].
• In this report, we investigated whether CHK is expressed in breast cancer tissues and whether it participates in the ErbB-2 signaling pathway in T47D and MCF-7 breast cancer cell lines [2].
• Overexpression of Bcl-2, Bcl-xL, or mutant DN-Fas-associated death domain protected HT29 cells from TRAIL-induced apoptosis in the presence of the CKI inhibitor [17].
• Apoptosis required caspase-9 and caspase-3 activity, and cytochrome c accumulated in the cytosol of CKI-treated cells [19].
• First, using a videomicroscopic motility assay, selective CKI inhibitors rescued dynein-driven microtubule sliding in axonemes isolated from paralyzed flagellar mutants lacking radial spokes [20].

Associations of CHKA with chemical compounds

• The activation of choline kinase and the increased levels of choline kinase alpha were partly responsible for the elevated phosphocholine levels [21].
• The Csk-homologous kinase (CHK), formerly MATK, is a tyrosine kinase that contains the Src homology 2 and 3 (SH2 and SH3) domains and demonstrates homology ( approximately 50%) to the Csk tyrosine kinase [2].
• To study the role of CHK in the ErbB-2 signaling pathway, glutathione S-transferase fusion proteins containing the SH2 and SH3 domains of CHK were generated [2].
• These observations suggest that lovastatin causes a profound cell cycle-independent alteration of CKI expression which is distinct from growth factor deprivation or thymidine block [22].
• The role of C-kinase in the induction of maturation of HL-60 promyelocytic leukemia cells was examined using two activators of this kinase, 12-O-tetradecanoyl phorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) [23].

Enzymatic interactions of CHKA

• These results indicate that, in A431 cells exposed to tumor promoters, C-kinase catalyzes phosphorylation of a significant population of EGF receptor molecules [24].

Other interactions of CHKA

• METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida [1].
• Protein kinase C-regulated dynamitin-macrophage-enriched myristoylated alanine-rice C kinase substrate interaction is involved in macrophage cell spreading [25].
• We report here a specific interaction between the cytoplasmic domain of IFN-alphaRbetaL and a previously identified protein, RACK-1 (receptor for activated C kinase) [26].
• These data are consistent with a model in which two branches of the Ca2+ messenger system participate in the action of TRH, a calmodulin branch and a C-kinase branch that interact to cause large amounts of sustained release [27].

Analytical, diagnostic and therapeutic context of CHKA

• In vivo association of the tyrosine-phosphorylated ErbB-2 with CHK was observed in co-immunoprecipitation studies with anti-CHK antibodies [2].
• Recombinant CKI was able to phosphorylate mTNF that had been dephosphorylated by sTNFR ligation in vivo, and this was less effective if phosphatase inhibitors had been used to prevent mTNF dephosphorylation [28].
• Third, Western blots indicate that within flagella, CKI is anchored exclusively to the axoneme [20].
• Confocal microscopy analysis revealed co-localization of CHK with ErbB-2 in these primary specimens (6/6) [29].
• Southern blot analysis showed that there was no other region homologous to the CK/EK-beta gene in the whole human genome [30].

References