JAK2 is required for GH-mediated phosphorylation of STATs 1,3,5A and 5B (Smit et al.1996). Some STAT activation may be mediated by direct association of JAK and STAT but maximal activation requires binding of STATs to phosphorylated tyrosines of the receptor (Smit et al. 1996, Lichanska & Waters 2006). Studies using mouse GHR truncated at K391, equivalent to human K380, suggest that STAT5 signaling is mediated by distal tyrosines, with 70% of the signaling lost if the receptor is truncated at P569, equivalent to human P558 (Rowland et al. 2005). Wang et al. (1996) using the porcine receptor found that phosphorylation at any one of the positions Y487, Y534, Y566 or Y627 (numbering identical in humans) was sufficient to allow STAT5 phosphorylation. Smit et al. (1996) identified mouse residues Y341 (human Y332) and Y346 (not conserved in human) as required for STAT1, 3, and maximal STAT5 activation.