Disease relevance of ICK

• With regard to other carcinomas, ICK (50.0%) and SCK (47.1%) gave better results than did RCK (30.6%) [1].

High impact information on ICK

• MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation [2].
• MRK preferentially phosphorylates R-P-X-S/T-P sites, with the preference for arginine at position -3 (P-3) being more stringent than for prolines at P-2 and P+1 [2].
• The calculated structure of Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that consists of a compact disulfide-bonded core from which four loops emerge [3].
• Although the C-terminal double-stranded beta-sheet cross-linked by two disulfide bonds (II-V and IV-VI in HWTX-II, II-V and III-VI in the ICK molecules) is conserved both in HWTX-II and the ICK molecules, the structure of HWTX-II is unexpected absence of the cystine knot because of its unique disulfide linkage [4].
• Using CLSM a strong fluorescence on the apical side of Caco-2 cell monolayers was observed, as a result of incubation with MRK 16 as primary and IgG Cy5 as secondary antibody [5].

Biological context of ICK

• Using the consensus, we identified a putative phosphorylation site (RPLT(1080)S) for MRK in human Scythe, an antiapoptotic protein that interacts with MRK [2].
• The hMRK was located at chromosome 6p12.3 by RH-PCR analysis [6].
• The norms were determined for the activity of peritoneal macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK) and human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK) [7].
• This suggest that in a subset of CLL patients post translational modification of the protein occurs masking the epitope recognized by MRK 16 [8].

Anatomical context of ICK

• The full-length hMRK protein was fused to C-terminal of GFP and expressed in Hela cells [6].
• The hMRK was generally expressed a single approximately 6.3 kb transcript at a low level in a variety of tissues except at a high level in testis [6].
• The depressed monocyte function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05) was observed indicating a compromised host defense [7].
• Specialized localization of P-glycoprotein recognized by MRK 16 monoclonal antibody in endothelial cells of the brain and the spinal cord [9].
• This communication describes the cellular and ultrastructural localization in the central nervous system of P-glycoprotein (P-GP) recognized by a murine monoclonal antibody, MRK 16 [9].

Associations of ICK with chemical compounds

• Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01) [10].
• Likewise, Curcumin and ICK suppressed NF-kappaB activation, but this did not reach significance in this experiment [10].
• The following information was collected: hours between pain onset and streptokinase administration (TS), hours of pain after streptokinase administration (DP), initial and peak creatine phosphokinase levels (ICK and PCK), time to peak creatine phosphokinase, time to electrocardiographic ST segment resolution [11].

Analytical, diagnostic and therapeutic context of ICK

• MRK phosphorylates Scythe at T1080 in vitro as determined by site-directed mutagenesis and mass spectrometry, supporting the consensus and suggesting Scythe as a physiological substrate for MRK [2].
• A novel human kinase gene, human MRK (hMRK), was cloned by using degenerate RT-PCR [6].
• We have studied the expression of this p-glycoprotein in chronic lymphatic leukaemia measured by immunofluorescence using a monoclonal antibody MRK 16 by flow cytometry [8].

References