Membrane receptor signaling by various ligands, including interferons and growth hormones such as EGF, induces activation of Jak kinases which then leads to tyrosine phosphorylation of the various Stat transcription factors. Stat1 and Stat2 are induced by IFN-a and form a heterodimer which is part of the ISGF3 transcription factor complex. Although early reports indicate Stat3 activation by EGF and IL-6, it has been shown that Stat3β appears to be activated by both while Stat3α is activated by EGF, but not by IL-6. Highest expression of Stat4 is seen in testis and myeloid cells. IL-12 has been identified as an activator of Stat4. Stat5 has been shown to be activated by prolactin and by IL-3. Stat6 is involved in IL-4 activated signaling pathways.