Bombesin modulates the association of Src with a nuclear 110-kd protein expressed in dividing prostate cells.
Polyclonal antibodies produced against a peptide derived from the Fer tyrosine kinase sequence also specifically recognized a 110-kd protein (p110) up-regulated in dividing versus resting dog prostate epithelial cells in vitro. In vivo in the dog prostate, p110 expression was detected when basal cell metaplasia was induced by estrogens after castration but not when renewing the differentiated epithelium with androgens. It was also detected in extracts from the human prostatic carcinoma cell lines LNCaP, DU145, and PC-3, and from 6 out of 11 human prostate cancer tissues analyzed, but not from normal or hyperplastic glands. The tyrosine kinase Src was shown by coimmunoprecipitation to associate with p110, and this interaction was positively modulated by bombesin stimulation of PC-3 cells. However, p110 was not tyrosine phosphorylated. Moreover, it was mainly distributed in the nuclear fraction. This nuclear p110 protein, expressed in dividing prostate epithelial cells and in human prostate cancer cells and tissues, could thus be a downstream mediator of bombesin-signaling pathways, acting via its association with Src.
Allard
P
P
Department of Biochemistry, University of Montreal, Quebec, Canada.
Beaulieu
P
P
Aprikian
A
A
Chevalier
S
S
D000818:Animals; D000918:Antibody Specificity; D000951:Antigens, Neoplasm; D015153:Blotting, Western; D001839:Bombesin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology; D003429:Cross Reactions; D004285:Dogs; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011467:Prostate / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D019061:src-Family Kinases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000951:Antigens, Neoplasm; D000939:Epitopes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C416530:SART3 protein, human; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D001839:Bombesin