Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase.
Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligand-activated tyrosine kinase in intracellular signaling by growth hormone (GH). Here we identify JAK2, a nonreceptor tyrosine kinase, as a GHR-associated tyrosine kinase. Immunological approaches were used to establish GH-dependent complex formation between JAK2 and GHR, activation of JAK2 tyrosine kinase activity, and tyrosyl phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2-erythropoietin receptor interactions described here and in the accompanying paper provide a molecular basis for involvement of tyrosyl phosphorylation in physiological responses to these ligands and suggest a shared signaling mechanism among members of the cytokine/hematopoietin receptor family.
Argetsinger
L S
LS
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Campbell
G S
GS
Yang
X
X
Witthuhn
B A
BA
Silvennoinen
O
O
Ihle
J N
JN
Carter-Su
C
C
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D013006:Growth Hormone / Q000378:metabolism*; D053614:Janus Kinase 2; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D014443:Tyrosine; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2