The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons.
Shc proteins possess SH2 and PTB domains and serve a scaffolding function in signaling by a variety of receptor tyrosine kinases. There are three known mammalian Shc genes, of which ShcB and ShcC are primarily expressed in the nervous system. We have generated null mutations in ShcB and ShcC and have obtained mice lacking either ShcB or ShcC or both gene products. ShcB-deficient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, which is not enhanced by additional loss of ShcC. Mice lacking both ShcB and ShcC exhibit a significant loss of neurons within the superior cervical ganglia, which is not observed in either mutant alone. The results indicate that these Shc family members possess both unique and overlapping functions in regulating neural development and suggest physiological roles for ShcB/ShcC in TrkA signaling.
Sakai
R
R
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada.
Henderson
J T
JT
O'Bryan
J P
JP
Elia
A J
AJ
Saxton
T M
TM
Pawson
T
T
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018390:Gene Targeting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides; D009928:Organ Specificity; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011506:Proteins; C122029:SHC3 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; C486295:Shc2 protein, mouse; C485682:Shc3 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D019000:Phosphotyrosine