Reactome | JAK2 phosphorylation of GHR

JAK2 phosphorylation of GHR

Stable Identifier

R-HSA-982807

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Activated JAK2 phosphorylates multiple tyrosine residues on GHR (Argetsinger et al. 1993, VanderKuur et al. 1994) including Y332 (VanderKuur 1995), Y487, Y534, Y566, and Y627 (Wang et al. 1996). Wang et al. using the porcine receptor found that phosphorylation at any of the positions they examined (all conserved in humans) was sufficient for STAT5 phosphorylation. While STAT5 activation requires phosphorylation of the distal region of GHR, this has no effect on STAT1 or STAT3 activation (Yi et al. 1996) suggesting different mechanisms. Mutation of Y332 to F in a truncated form of GHR with only the first 54 residues of the cytoplasmic domain had no effect on JAK2 activation or cell proliferation presumed to be mediated by ERK (Wang et al. 1995) so the significance of phosphorylation at this position is unclear. SHP2 binds to Y595 of rat GHR (identical numbering in humans) and to a lesser extent Y487; mutation of these residues impairs the association (Stofega et al. 2000). SOCS3 binds to rat GHR Y333 (equivalent of human Y332), Y338 (not conserved in humans) (Ram & Waxman 1999) and Y487 (Hansen et al. 1999). SOCS-1 has been implicated as a direct inhibitor of JAK kinases (Yasukawa et al. 1999). This reaction represents the phosphorylation of all GHR tyrosines known to be phosphorylated by JAK2.

Literature References

PubMed ID	Title	Journal	Year
3349036	Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytes Foster, CM, Shafer, JA, Rozsa, FW, Wang, XY, Lewis, SD, Renken, DA, Natale, JE, Schwartz, J, Carter-Su, C	Biochemistry	1988
7691587	Human growth hormone (GH) receptor is characterized as the 134-kilodalton tyrosine-phosphorylated protein activated by GH treatment in IM-9 cells Silva, CM, Day, RN, Weber, MJ, Thorner, MO	Endocrinology	1993