A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-erbB signaling to actin stress fiber disassembly.
The avian erythroblastosis viral oncogene (v-erbB) encodes a receptor tyrosine kinase that possesses sarcomagenic and leukemogenic potential. We have expressed transforming and nontransforming mutants of v-erbB in fibroblasts to detect transformation-associated signal transduction events. Coimmunoprecipitation and affinity chromatography have been used to identify a transformation-associated, tyrosine phosphorylated, multiprotein complex. This complex consists of Src homologous collagen protein (Shc), growth factor receptor binding protein 2 (Grb2), son of sevenless (Sos), and a novel tyrosine phosphorylated form of the cytoskeletal regulatory protein caldesmon. Immunofluorescence localization studies further reveal that, in contrast to the distribution of caldesmon along actin stress fibers in normal fibroblasts, caldesmon colocalizes with Shc in plasma membrane blebs in transformed fibroblasts. This colocalization of caldesmon and Shc correlates with actin stress fiber disassembly and v-erbB-mediated transformation. The tyrosine phosphorylation of caldesmon, and its association with the Shc-Grb2-Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes, and may define one mechanism regulating actin stress fiber disassembly in transformed cells.
McManus
M J
MJ
Division of Pediatric Hematology/Oncology, The Mayo Clinic, Rochester, MN 55905, USA.
Lingle
W L
WL
Salisbury
J L
JL
Maihle
N J
NJ
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis; D005347:Fibroblasts; D051380:GRB2 Adaptor Protein; D018815:Genes, erbB; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002148:Calmodulin-Binding Proteins; D051380:GRB2 Adaptor Protein; D018739:Oncogene Proteins v-erbB; D011506:Proteins; D011993:Recombinant Fusion Proteins; D003094:Collagen; D066246:ErbB Receptors