Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis

Abstract

Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron-exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.

Genome‐Wide Transcriptional Analysis Reveals the Protection against Hypoxia‐Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

“…Furthermore, our network also shows the close relationship among GRB2, EGFR, and PTPN11 pathways (Figure 9), which is accordant with previous reports [68, 69] except of PTPN11 pathway. Further work is needed to confirm the detailed relation among the three pathways.…”

Global Profiling of PknG Interactions Using a Human Proteome Microarray Reveals Novel Connections with CypA

“…HRAS also acts as a molecular switch in processes of the cell proliferation, differentiation, survival, and death . GRB2 is also a key regulator in RAS signaling . Two MAPK related proteins, MAPK3 and MAPK9, were also found in the PknG–human protein interaction network.…”

“…[30] GRB2 is also a key regulator in RAS signaling. [31] Two MAPK related proteins, MAPK3 and MAPK9, were also found in the PknG-human protein interaction network. The MAPK1/3 pathway is activated by extracellular and intracellular mitogenic stimuli and has crucial roles in cellular differentiation, proliferation, and survival.…”

Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways

“…These have functions as molecular switches for signaling pathways regulating cell proliferation, survival, migration, differentiation and cytoskeletal dynamism. 34 However, in reality, many other proteins are also involved in this pathway, including EGFR, 35 GRB2, 36 and VEGF and the PDGF family. 37, 38 A number of researchers have demonstrated that upon stimulation with growth factors, or other inputs, the Ras/MAPK system can promote cell proliferation, differentiation and/or migration.…”