Decreased Phosphorylated ERK 1/2 in Individuals with Autism

Anthony Russo,Judith Bowman,Albert Mensah

doi:10.18314/ipcc.v2i1.1688

Abstract

Autism spectrum disorders (ASDs) are complex, highly heritable neurodevelopmental disorders affecting ∼1 in 60-100 children. The extracellular signal-regulated kinases, ERK1 and ERK2, are central elements of one of the most prominent intracellular signaling cascades, the mitogen activated protein kinase (MAPK) pathway. They are genetically linked to ASDs and other syndromes typified by intellectual disability. In this study, we measured the concentration of phosphorylated (activated) ERK 1 and 2. We present evidence that ERK is decreased in individuals with autism, and that ERK levels are associated with decreased Epidermal Growth Factor Receptor (EGFR).

Highlights

Growth factors, through receptor tyrosine kinases, recruit a large network of signaling proteins to execute their cellular programs
Copy number variations (CNVs) of human chromosome 16p11.2 is one of the most common genetic linkages to autism and deletion of this region accounts for ∼1% of Autism spectrum disorders (ASDs) [3], demonstrated by the fact that individuals heterozygous for the 16p11.2 deletion exhibit a range of clinical symptoms including ASD, language impairment, intellectual disability (ID), anxiety, attention deficit hyperactivity disorder and epilepsy [4,5,6]
We found that there was a negative correlation between the phosphorylated ERK 1 and 2 levels and Epidermal Growth Factor Receptor (EGFR) (r=-0.45; p=0.04)

Summary

Introduction

Through receptor tyrosine kinases, recruit a large network of signaling proteins to execute their cellular programs. The ERK phosphorylation cascade is linked to cell surface receptor tyrosine kinases (RTKs) (11). Copy number variations (CNVs) and other chromosomal rearrangements are associated with ∼10-20% of ASDs. CNV of human chromosome 16p11.2 is one of the most common genetic linkages to autism and deletion of this region accounts for ∼1% of ASDs [3], demonstrated by the fact that individuals heterozygous for the 16p11.2 deletion exhibit a range of clinical symptoms including ASD, language impairment, intellectual disability (ID), anxiety, attention deficit hyperactivity disorder and epilepsy [4,5,6].

Results

Conclusion