Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl.
A novel C3G isoform, designated p87C3G, lacking the most amino terminal region of the cognate protein has been found to be overexpressed in two CML cell lines, K562 and Boff 210, both expressing Bcr-Abl p210. p87C3G expression is also highly augmented in patients diagnosed with chronic myeloid leukemia (CML) Ph+, in comparison with healthy individuals, and returns to basal levels after treatment with STI571. p87C3G co-immunoprecipitates with both CrkL and Bcr-Abl in CML cell lines and co-immunoprecipitation between p87C3G and Bcr-Abl was also detected in primary cells from CML patients. These interactions have been confirmed by in vitro pull down experiments. The interaction between p87C3G and Bcr-Abl involves the SH3-binding domain of p87C3G and the SH3 domain of Abl and depends mostly on the first polyproline region of p87C3G. Furthermore, we also demonstrated that p87C3G is phosphorylated in vitro by a Bcr-Abl-dependent mechanism. These results indicate that p87C3G overexpression is linked to CML phenotype and that p87C3G may exert productive functional interactions with Bcr-Abl signaling components suggesting the implication of this C3G isoform in the pathogenesis of chronic myeloid leukemia.
Gutiérrez-Berzal
Javier
J
Centro de Investigación del Cáncer, IBMCC, Universidad de Salamanca-CSIC, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Castellano
Esther
E
Martín-Encabo
Susana
S
Gutiérrez-Cianca
Noelia
N
Hernández
Jesús M
JM
Santos
Eugenio
E
Guerrero
Carmen
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D016044:Fusion Proteins, bcr-abl; D015973:Gene Expression Regulation, Leukemic; D016313:Genes, abl / Q000235:genetics; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D020735:Guanine Nucleotide-Releasing Factor 2; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl