Disease relevance of MAK

• Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells [1].
• Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNF alpha) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF alpha (MAK 195F) [2].
• Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study [3].
• OBJECTIVE: The aim was to determine the ability of macrophage-activated killer cells (MAK cells) obtained from peripheral blood of normal volunteers to kill glioblastoma multiforme (GBM) cell lines [4].
• Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2 [5].

High impact information on MAK

• MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation [6].
• We isolated a novel gene designated mak (male germ cell-associated kinase) by using weak cross-hybridization with a tyrosine kinase gene (v-ros) [7].
• Furthermore, MAK was recruited to the cell membrane by Frizzled 3, formed a complex with Dishevelled and phosphorylated Dsh in vitro [8].
• Confirming the inhibitory role for this kinase in Wnt/beta-catenin signaling, the midbrain patterning defects in embryos depleted of MAK were rescued by the simultaneous depletion of beta-catenin [8].
• In contrast, hMAK expression was decreased only in the presence of dihydrotestosterone after androgen receptor knock-down [9].

Chemical compound and disease context of MAK

• Disinfections to prevent notifiable infectious diseases in accordance with the Federal Epidemic Law (Bundesseuchengesetz) involving the use of higher disinfectant concentrations are liable to exceed the MAK limits for formaldehyde and glutardialdehyde [10].

Biological context of MAK

• A reverse transcription-PCR product encompassing the entire hMAK open reading frame was isolated [1].
• A 3.7-kilobase pair promoter of the hMAK locus was isolated from a human genomic DNA bacterial artificial chromosome clone and was shown to be activated by DHT [1].
• The results from sequencing analysis showed that the hMAK protein is 623 amino acids in length and contains a kinase catalytic domain at its N terminus, followed by a proline/glutamine-rich domain [1].
• Mouse Mak gene for male germ cell-associated kinase maps to chromosome 13 [11].
• In situ localization of male germ cell-associated kinase (mak) mRNA in adult mouse testis: specific expression in germ cells at stages around meiotic cell division [12].

Anatomical context of MAK

• In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures [13].
• The expression levels of hMAK in prostate cancer cell lines are in general higher than those of normal prostate epithelial cells [1].
• Biochemical analysis of the male germ cell-associated kinase (mak) gene, which was isolated recently by using weak cross-hybridization with the v-ros tyrosine kinase gene, revealed that the gene was highly expressed in mammalian testicular germ cells, but not in ovarian cells [12].
• In all but one case, both the metaplastic and glandular epithelium had positive results for MAK 6 and CK-KES [14].
• Thus, we propose that three enzymes could account for the N-methylated species so far identified in bacteria, the hypothetical MAK, QP, and pilin methyltransferases, and a single additional enzyme, the hypothetical PK methyltransferase, could account for all of the alpha-amino methylations observed in eukaryotic cells [15].

Associations of MAK with chemical compounds

• Real time reverse transcription-PCR studies demonstrated a 9-fold induction of hMAK by 10 nm DHT at 24 h post-stimulation [1].
• Using a novel kinase display approach, we have identified a protein kinase, human male germ cell-associated kinase (hMAK), which is transcriptionally induced by the androgenic hormone 5alpha-dihydrotestosterone (DHT) [1].
• METHODS: Monocytes, from leukapheresis product, were isolated by countercurrent elutriation and differentiated into MAK cells by culture with granulocyte/macrophage-colony-stimulating factor, vitamin D3 and interferon gamma [4].
• We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable [16].
• Occupational styrene exposure near the MAK-value (100 ppm) results in a L/D-enantiomer-ratio in urine of nearly 1.5 [17].

Other interactions of MAK

• Our data speak against a modulation of coagulation or the fibrinolytic system by the monoclonal anti-TNF alpha antibody MAK 195F in this cohort of sepsis patients [18].
• Cytokeratins (AE1/AE3 and MAK 6) were strongly positive in all cases stained [19].
• Cloning and Sequence Analysis of the 22-kDa Antigen Genes of Orientia tsutsugamushi Strains Kato, TA763, AFSC 7, 18-032460, TH1814, and MAK 119 [20].

Analytical, diagnostic and therapeutic context of MAK

• The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK [16].
• Combined effectors, targets and bsAb were incubated and the percentage of MAK cells with phagocytosed targets was determined by flow cytometry [4].
• Therefore, intracavity MAK cells armed with MDX-447 could be an effective adoptive immunotherapy for EGFR-positive GBM [4].
• We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer [16].
• Low amounts of activated macrophages (MAK) caused regression of experimental tumors in animal models [21].

References