👤 Aleksandra Jurek

Dyslexia, a heterogeneous neurodevelopmental disorder, is characterized by persistent reading and spelling difficulties despite average intellectual potential. Although intellectual functioning in dyslexia is often described as average, emerging evidence suggests meaningful within-group variability. This study examined whether children and adolescents with dyslexia exhibited distinct intellectual profiles based on the Stanford-Binet Intelligence Scales, Fifth Edition (SB5). Data were obtained from a large, diagnostically verified sample of 3458 individuals aged 10-19 years assessed in psychological-pedagogical counseling centers across Poland. We used latent profile analysis (LPA) of all 10 SB5 subtests and compared models that specified 2-6 latent classes. The optimal solution identified two profiles: (a) a small subgroup (5%) with globally reduced intellectual functioning and a profound deficit in verbal working memory (>3 standard deviations below the norm) and (b) the predominant subgroup (95%) with broadly average intellectual functioning and relatively preserved reasoning abilities. Profile membership was associated with socioeconomic status; the low-functioning subgroup was associated with lower parental education and age, as younger participants were more likely to belong to this group. These findings highlight the dimensional nature of intellectual heterogeneity in dyslexia and underscore the diagnostic value of profile-based approaches over global intelligence quotient (IQ) scores. Show less

MAPK phosphatases (MKPs) are dual specificity phosphatases that dephosphorylate and thereby inactivate MAPKs. In the present study, we provide evidence that platelet-derived growth factor BB (PDGF-BB) regulates MKP3 (DUSP6), which is considered to be a phosphatase highly selective for Erk. Intriguingly, we observed that Mek is positively regulated by MKP3, whereas Erk itself is negatively regulated. In addition, we found that activation of PDGF receptor alpha or beta leads to a rapid proteasomal degradation of MKP3 in a manner that requires Mek activation; this feed-forward mechanism was found to be essential for efficient Erk phosphorylation. We could also demonstrate that PDGF-BB stimulation induces phosphorylation of MKP3 at Ser-174 and Ser-300; phosphorylation of Ser-174 is involved in PDGF-induced MKP3 degradation, since mutation of this site stabilized MKP3. Moreover, activated Erk induces mkp3 expression, leading to restoration of MKP3 levels after 1-2 h and a concomitant dephosphorylation of Erk in cells with activated PDGFRalpha. Reducing the MKP3 level by small interfering RNA leads to an increased Erk activation and mitogenic response to PDGF-BB. In conclusion, MKP3 is an important regulator of PDGF-induced Erk phosphorylation acting in both a rapid positive feed-forward and a later negative feed-back loop. Show less