MAK (male germ cell-associated protein kinase) and MRK/ICK (MAK-related kinase/intestinal cell kinase) are human homologs of Ime2p in Saccharomyces cerevisiae and of Mde3 and Pit1 in Schizosaccharomyces pombe and are similar to human cyclin-dependent kinase 2 (CDK2) and extracellular signal-regulated kinase 2 (ERK2). MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation. Herein, we establish that human CDK-related kinase CCRK (cell cycle-related kinase) is an activating T157 kinase for MRK, whereas active CDK7/cyclin H/MAT1 complexes phosphorylate CDK2 but not MRK. Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ. Thus, CCRK and PP5 are yin-yang regulators of T157 phosphorylation. To determine a substrate consensus, we screened a combinatorial peptide library with active MRK. 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. Using the consensus, we identified a putative phosphorylation site (RPLT 1080 S) for MRK in human Scythe, an antiapoptotic protein that interacts with MRK. 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.
Current hypotheses explaining the link between learning disability and delinquency are reviewed and evaluated. Research from diverse fields is integrated and an alternative hypothesis is proposed to explain the link between learning disability and delinquency. The alternative hypothesis postulates that ineffective social cognitive problem-solving skills increase risk for delinquency in learning disabled youth. Future research is suggested.
The efficacy of social metacognitive training focusing on impulse control, metacognitive awareness, and metacognitive control for enhancing overt social adjustment in delinquent youth was examined. Learning disabled (LD, n = 34) and low-achieving (NLD, n = 34) incarcerated delinquents (16 to 19 years) were assigned randomly to social metacognitive training, attention control or test-only control groups. Institutional staff and subjects were blind to both experimental conditions and variable measures. Compared to subjects in attention and test-only control conditions, those given metacognitive training showed significant improvements in (a) quantity of negative behavior reports, (b) staff ratings on rehabilitation achievement, and (c) institutional living unit phase level promotions. Although both LD and NLD delinquents who received cognitive training significantly improved their behavior, on every variable the LD group had a greater proportion of subjects improve. Parallel improvement in metacognitive skills and significant correlations between social metacognitive scores and indicators of effective behavior support the notion that social metacognition was the “mechanism” of treatment and that social metacognition mediates overt social behavior in novel contexts without specific cueing from the environment. Results are interpreted within the context of a series of studies testing the hypothesis that social metacognitive deficits increase risk for maladaptive behavior, including delinquency, in LD youth.
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