Receptor tyrosine kinases (RTKs) control a wide variety of processes in multicellular organisms, including proliferation, differentiation, migration and survival.

Their activity is tightly controlled through the coordinated action of both positive and negative regulators that function at multiple levels of the signal transduction cascade, and at different time points within the growth-factor-induced response. When this process goes awry, the outcome can be developmental defects and malignancy.

Types

 Src kinases family
 ephrins (EPHs) and ephrin receptors (EPHRs)
 sprouty proteins

Mutations

 loss-of-function mutations
 gain-of-function mutations

Pathology

 dwarfism
 craniosynostosis
 heritable cancer susceptibility syndromes
 venous malformation
 piebaldism
 cancer

• The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors and is often associated with the acquisition of an aggressive phenotype.

References

 Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med. 2005 Jul 14;353(2):172-87. PMID: #16014887#

 Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004 May;4(5):361-70. PMID: #15122207#

 Gu H, Neel BG. The 'Gab' in signal transduction. Trends Cell Biol. 2003 Mar;13(3):122-30. PMID: #12628344#

 Zwick E, Bange J, Ullrich A. Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med. 2002 Jan;8(1):17-23. PMID: #11796262#

 Ostman A, Bohmer FD. Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol. 2001 Jun;11(6):258-66. PMID: #11356362#

 Robertson SC, Tynan JA, Donoghue DJ. RTK mutations and human syndromes when good receptors turn bad. Trends Genet. 2000 Jun;16(6):265-71. PMID: #10827454#

 Tan PB, Kim SK. Signaling specificity: the RTK/RAS/MAP kinase pathway in metazoans. Trends Genet. 1999 Apr;15(4):145-9. PMID: #10203824#