Autophosphorylation, internalization, and nuclear localization of activated KIT with tyrosine phosphorylation at 568/570 (pY568/pY570KIT).

<p>(<b><i>A</i></b>), IHC of frozen sections of an aggressive GIST (<i>a-c</i>) and a normal human adult testis as external control (<i>d-f</i>) using pan-KIT antibody (<i>a</i> and <i>d</i>), pY568/pY570KIT antibody (b and <i>e</i>, red arrow indicates nuclear localization), and pY703KIT antibody (<i>c</i> and <i>f</i>) respectively. (<b><i>B</i></b>), <i>In situ</i> IHC to assess kinetics of SCF-induced nuclear translocation of pY568/pY570KIT using WM793 melanoma cells cultured in 4-well chamber tissue culture treated glass slides. Control (<i>g)</i> without SCF stimulation, after addition of SCF to culture media, the nuclear localization of pY568/pY570KIT increases progressively (<i>h-j</i>) in more than 90% of WM793 cells, reaches a plateau about 40–60 minutes (<i>i</i> and <i>j</i>), begins to decrease at 90 minutes (<i>k</i>), and is completely absent in nucleus with relocation back to the cytoplasm at 4 hours, some residual cytoplasmic staining remains visible (<i>l</i>).</p

Immunohistochemical studies on human colon myenteric plexus demonstrate that 48 hours fasting results in activation of SCF-KIT signaling and concomitant parallel induction of endothelin-3.

<p>Human colon specimens post 48 hours fasting demonstrate intense KIT staining in ICCs within the myenteric plexus (<i>a</i>), and intense ET3 staining within the myenteric plexus (<i>b</i>). In sharp contrast, the surrounding longitudinal and circular smooth muscle cells (SM) show negative ET3 staining.</p