Receptor tyrosine kinases (RTKs) are important in the transmission of biochemical signals across the plasma membrane of cells.  These transmembrane molecules characteristically consist of an extracellular ligand-binding domain connected through a segment in the plasma membrane to an intracellular tyrosine kinase domain. 
The human epidermal growth factor receptor (HER) family consists of four distinct receptor tyrosine kinases referred to HER1, HER2, HER3, and HER4.  These kinases are also referred to as erbB1, erbB2, etc.  HER1 is also commonly referred to as the epidermal growth factor (EGF) receptor.  With the exception of HER3, these receptors have intrinsic protein kinase activity that is specific for tyrosine residues of phosphoacceptor proteins.  The HER kinases are expressed in most epithelial cells as well as tumor cells of epithelial origin.  They are also often expressed in tumor cells of mesenchymal origin such as sarcomas or rhabdomyosarcomas.  RTKs such as HER1 and HER2 are involved in cell proliferation and are associated with diseases such as psoriasis and cancer.  Disruption of signal transduction by inhibition of these kinases would have an antiproliferative and therapeutic effect. 
The enzymatic activity of receptor tyrosine kinases can be stimulated by either overexpression, or by ligand-mediated dimerization.  The formation of homodimers as well as heterodimers has been demonstrated for the HER receptor family.  An example of homodimerization is the dimerization of HER1 (EGF receptor) by one of the EGF family of ligands (which includes EGF, transforming growth factor alpha, betacellulin, heparin-binding EGF, and epiregulin).  Heterodimerization among the four HER receptor kinases can be promoted by binding to members of the heregulin (also referred to neuregulin) family of ligands.  Such heterodimerization as involving HER2 and HER3, or a HER3/HER4 combination, results in a significant stimulation of the tyrosine kinase activity of the receptor dimers even though one of the receptors (HER3) is enzymatically inert.  The kinase activity of HER2 has been shown to be activated also by virtue of overexpression of the receptor alone in a variety of cell types.  Activation of receptor homodimers and heterodimers results in phosphorylation of tyrosine residues on the receptors and on other intracellular proteins.  This is followed by the activation of intracellular signaling pathways such as those involving the microtubule associated protein kinase (MAP kinase) and the phosphatidylinositol 3-kinase (PI3 kinase).  Activation of these pathways have been shown to lead to cell proliferation and the inhibition of apoptosis.  Inhibition of HER kinase signaling has been shown to inhibit cell proliferation and survival. 
Tropomysosin Related Kinases (Trk) are a family of receptor tyrosine kinases composed of three family members, TrkA, TrkB and TrkC. The Trks bind with high affinity and mediate the signal transduction of the Neurotrophin family of ligands whose prototype member is Nerve Growth Factor (NGF).  In addition, a co-receptor lacking enzymatic activity, p75, has been identified which binds all NTs with low affinity and regulates neurotrophin signaling.  A critical role of the Trks and their ligands during the development of the central and peripheral nervous systems have been established through gene disruption studies in mice.  In particular, TrkA-NGF interaction was shown as a requirement for the survival of certain peripheral neuron populations involved in mediating pain signaling.  In addition to these developmental consequences of Trk signaling, the subversion of this receptor and its signaling pathway in certain malignancies has also been documented.  Of particular note are reports of activating chromosomal rearrangements of Trks in thyroid and breast cancers and receptor point mutations predicted to be constitutively activating in colon tumors.  In addition to these activation mechanisms, elevated Trk receptor and ligand have also been reported in a variety of tumor types including multiple myeloma, melanoma, and pancreatic canrcinoma.  The oncogenic properties of Trk signaling in multiple tumor types makes the modulation of the Trk receptor signaling a potentially attractive therapeutic intervention point in different malignancies. 
Other RTKs such as VEGFR-2 are associated with the proliferation of endothelial cells as well as tumor cells.  Disruption of this pathway would have an antiproliferative effect and a therapeutic effect on disorders related to vasculogenesis or angiogenesis.