<P> By 2004 , 58 receptor tyrosine kinases ( RTKs ) were known , grouped into 20 subfamilies . They play pivotal roles in diverse cellular activities including growth ( by signaling neurotrophins ) , differentiation , metabolism , adhesion , motility , death . RTKs are composed of an extracellular domain , which is able to bind a specific ligand , a transmembrane domain , and an intracellular catalytic domain , which is able to bind and phosphorylate selected substrates . Binding of a ligand to the extracellular region causes a series of structural rearrangements in the RTK that lead to its enzymatic activation . In particular , movement of some parts of the kinase domain gives free access to adenosine triphosphate ( ATP ) and the substrate to the active site . This triggers a cascade of events through phosphorylation of intracellular proteins that ultimately transmit ( `` transduce '' ) the extracellular signal to the nucleus , causing changes in gene expression . Many RTKs are involved in oncogenesis , either by gene mutation , or chromosome translocation , or simply by over-expression . In every case , the result is a hyper - active kinase , that confers an aberrant , ligand - independent , non-regulated growth stimulus to the cancer cells . </P>
why does overexpression of rtks lead to cancer development
a hyper - active kinase , that confers an aberrant , ligand - independent , non-regulated growth stimulus to the cancer cells