Cancer, eye, kidney, skin, and neurological disorders

Trachoma; Corticobasal degeneration (CBGD); Congenital insensitivity to pain with anhidrosis (CIPA); Mesangial proliferative glomerulonephritis; Frozen shoulder; Retrograde amnesia

Trachoma is a rare infectious disease that affects the eye. Transmission is through direct contact with infected eye discharge. Corticobasal Degeneration (CBGD) is a rare neuronal disease characterized by neuronal loss and reduced brain size. Symptoms may be similar to Parkinson disease. CBGD can affect the cortex, whole brain, and eye tissues. The rare disorder Congenital Insensitivity to Pain with Anhidrosis (CIPA) is characterized by pain insensitivity and reduced or absent sweating. CIPA sufferers may have repeated bone infections and affected tissues can include bone and skin. Mesangial Proliferative Glomerulonephritis is a rare disease and is a form of Lupus Nephritis, which is the inflammation of the kidney. Anhidrosis is the decrease or fully impaired ability to sweat, leading to fever-related issues. Frozen Shoulder is characterized by inflammation of the shoulder, causing pain, and it is associated with diabetes mellitus and osteoarthritis. Frozen Shoulder can affect bone, skin, and testes. The K54R mutation does not inhibit MAP2K1-ERK2 interaction. The T185A and Y187A mutations, in conjunction, will inhibit ERK2 interaction with TPR, whereas L234A can inhibit a TPR complex by itself. PTPRJ-mediated phosphorylation of ERK2 is lost with a D318A mutation. MEK2 interaction with MAP2K1, but not TPR, is inhibited with the D318N+D321N mutations.
 

Breast cancer; Pancreatic cancer; Thyroid lymphomas; Ewing's Family of tumours; Distal 22q11.2 Microdeletion syndrome

ERK2 appears to be a tumour requiring protein (TRP). The active form of the protein kinase normally acts to promote tumour cell proliferation. ERK2 has been linked with the Ewing's Family of tumours, which are rare cancers that are similar to medullablastoma and cerebral primitive neuroectodermal tumours. Distal 22q11. 2 Microdeletion Syndrome is a rare fetal cancer disease, which is similar to B-cell chronic lymphocytic leukemia and myeloid leukemia.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= +65, p<0.002); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +223, p<0.088); Gastric cancer (%CFC= +74, p<0.008); Prostate cancer (%CFC= -54, p<0.016); and Uterine fibroids (%CFC= +62, p<0.025). The COSMIC website notes an up-regulated expression score for ERK2 in diverse human cancers of 439, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 355 for this protein kinase in human cancers was 5.9-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.09 % in 25487 diverse cancer specimens. This rate is only 22 % higher than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.41 % in 805 skin cancers tested; 0.3 % in 1093 large intestine cancers tested.

Most frequent mutations with the number of reports indicated in brackets: E332K (12).

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.