Reactome: A Curated Pathway Database

JAK2 phosphorylation of GHR

Stable Identifier
R-HSA-982807
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
Participants
Participant Of
This entity is regulated by:
Title Physical Entity Activity
protein tyrosine kinase activity of Growth Hormone: Activated Growth Hormone Receptor- p(Y1007)-JAK2 dimer [plasma membrane] Growth Hormone: Activated Growth Hormone Receptor- p(Y1007)-JAK2 dimer [plasma membrane] protein tyrosine kinase activity (0004713)
Orthologous Events