tyrosine kinases

Tyrosine kinases can be classified as either membrane associated receptors (receptor tyrosine kinases or RTKs) or intracellular nonreceptor molecules.

Protein tyrosine kinases (TKs) are enzymes that catalyze the transfer of phosphate from ATP to tyrosine residues in polypeptides.

The human genome contains about 90 TKs and 43 TK-like genes, the products of which regulate cellular proliferation, survival, differentiation, function, and motility.

Intracellular nonreceptor TKs

Intracellular nonreceptor TKs include BTK (300300), ITK (186973), TXK (600058), and BMX (300101).

Types

 receptor tyrosine kinases (RTKs)
 intracellular nonreceptor tyrosine kinases (INRTKs)

• BTK (MIM.300300)
• ITK (MIM.186973)
• TXK (MIM.600058)
• BMX (MIM.300101)

Therapeutics

More than 25 years ago, TKs were implicated as oncogenes in animal tumors induced by retroviruses. However, they were largely ignored in drug development because of a paucity of evidence for a causative role in human cancer and concerns about drug specificity and toxicity.

The landscape was changed radically by the success of imatinib mesylate, an inhibitor of the BCR-ABL TK in chronic myeloid leukemia (CML) — a result heralded as a proof-of-principle and a triumph of targeted cancer therapy.

TKs are now regarded as excellent targets for cancer chemotherapy, but reality lies somewhere between the extremes of triumph and tribulation. In this article we will review mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, summarize the status of TK-directed cancer therapies, and discuss challenges and prospects for the future.

See also

 protein kinases (PKs)
 tyrosine kinases inhibitors

References

 Lengyel E, Sawada K, Salgia R. Tyrosine kinase mutations in human cancer. Curr Mol Med. 2007 Feb;7(1):77-84. PMID: 17311534

 Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005;353:172-187.