Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses.
Ron receptor activation induces numerous cellular responses in vitro, including proliferation, dissociation, and migration. Ron is thought to be involved in blood cell development in vivo, as well as in many aspects of the immune response including macrophage activation, antigen presentation, and nitric oxide regulation. In previous studies to determine the function of Ron in vivo, mice were generated with a targeted deletion of the extracellular and transmembrane regions of this gene. Mice homologous for this deletion appear to die early during embryonic development. To ascertain the in vivo function of Ron in more detail, we have generated mice with a germline ablation of the tyrosine kinase domain. Strikingly, our studies indicate that this domain of Ron, and therefore Ron cytoplasmic signaling, is not essential for embryonic development. While mice deficient in this domain are overtly normal, mice lacking Ron signaling have an altered ability to regulate nitric oxide levels and, in addition, have enhanced tissue damage following acute and cell-mediated inflammatory responses.
Waltz
S E
SE
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA. swaltz@chmcc.org
Eaton
L
L
Toney-Earley
K
K
Hess
K A
KA
Peace
B E
BE
Ihlendorf
J R
JR
Wang
M H
MH
Kaestner
K H
KH
Degen
S J
SJ
D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology / Q000473:pathology; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000633:toxicity; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005804:Genes, Lethal; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D017228:Hepatocyte Growth Factor; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007509:Irritants / Q000633:toxicity; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D019800:Phenol / Q000633:toxicity; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016037:Single-Blind Method; D013312:Stress, Physiological / Q000150:complications
D006133:Growth Substances; D007509:Irritants; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C082332:macrophage stimulating protein; D019000:Phosphotyrosine; D009569:Nitric Oxide; D019800:Phenol; D017228:Hepatocyte Growth Factor; D004139:Dinitrofluorobenzene; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases