ABL (gene)

• OMIM: 189980
• UniProt: P00519
• MGI: 87859

The tyrosine kinase ABL1 ( Abelson murine leukemia viral acronym for oncogene homolog 1, also c- Abl, p150 ) is a different body cells occurring protein of the family of tyrosine kinases.

This protein is involved in many cellular processes such as cell migration, cell adhesion, cell differentiation, and apoptosis, and is an important element for signal transduction via T -cell receptor. c -Abl is the gene product of the proto-oncogene c -abl same name, a precursor of a potentially cancer-causing gene. Through exchange ( translocation ) of chromosome fragments between the c -abl harboring chromosome 9 and the bcr gene harboring chromosome 22, which can lead to the so-called Philadelphia chromosome, a new bcr -abl gene, the resulting first found by chromosome changes oncogene and was, among other things at 95 % of chronic myeloid leukemia (CML ) can be demonstrated. Therefore Abl proteins are popular targets for drug development.

Biochemistry

Structure

C -Abl is a protein with a molecular mass of about 145 kDa, which is encoded by a gene on chromosome 9 locus q34. This system consists of an SH2 and SH3 domains, which are responsible for regulation of c- Abl, and a function of carrying the enzyme kinase domain. The C-terminus carrying a binding domain for interaction with the DNA and actin. Due to the different splicing two different N -terminal protein sequences can be formed. The N-terminus of c -Abl, which additionally carries a myristylation site in the case of splice variant 1B is responsible for autoinhibition. A binding site for Myristinsäurereste could be identified in the C -lobe of the kinase function.

Activation and regulation

C -Abl is present in a basal inactive state. For the inactivity of the N-terminal part of the protein and is responsible myristyl, although the splice 1A has no such myristylation. However, also with fatty acids, modified proteins such as Fus1 to stabilize the inactive state, be involved. A complete absence of the terminal, such as in the case of the oncogene v -Abl viral descendant and mutant oncogenic BCR -Abl, has been associated with constitutive activity of the kinase function and carcinogenic potential.

C -Abl, by receptor Tyrosikinasen, such as the EGF receptor, and non- receptor tyrosine kinases, such as c- Src can be activated.

Further Reading

• Lin J, Arlinghaus R. (2008). Activated c -Abl tyrosine kinase in malignant solid tumors. Oncogene 27:4385-4391.