mitogen-activated protein kinase kinase 1
The MAP2K1 gene provides instructions for making a protein known as MEK1 protein kinase. This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. RAS/MAPK signaling helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). MEK1 protein kinase appears to be essential for normal development before birth and for survival after birth.
At least 13 mutations in the MAP2K1 gene have been identified in people with cardiofaciocutaneous syndrome. This condition affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). Each of these MAP2K1 gene mutations changes a single protein building block (amino acid) in MEK1 protein kinase. These genetic changes abnormally activate the protein, which disrupts the tightly regulated RAS/MAPK signaling pathway in cells throughout the body. The altered signaling interferes with the normal development of many organs and tissues, resulting in the characteristic features of cardiofaciocutaneous syndrome.
At least one mutation in the MAP2K1 gene has been found to cause Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome). This condition is characterized by multiple brown skin spots (lentigines), heart defects, short stature, a sunken or protruding chest, and distinctive facial features.
The identified MAP2K1 gene mutation replaces the amino acid glutamic acid with the amino acid glycine at position 102 (written as Glu102Gly or E102G) in MEK1 protein kinase. This change likely results in increased activation of the RAS/MAPK signaling pathway in cells throughout the body. The increased signaling interferes with the normal development of many organs and tissues, resulting in the characteristic features of Noonan syndrome with multiple lentigines.
It is unclear why the E102G mutation causes Noonan syndrome with multiple lentigines and other MAP2K1 gene mutations cause different disorders, such as cardiofaciocutaneous syndrome (described above).
Genetics Home Reference provides information about Langerhans cell histiocytosis.
Genetics Home Reference provides information about lung cancer.
Genetics Home Reference provides information about Noonan syndrome.
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1
- ERK Activator Kinase 1
- MAP Kinase Kinase 1
- MAPK/ERK kinase 1
- MEK-1 Protein Kinase
- MKK-1 Protein Kinase
- MKK1 Protein Kinase
- protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)