SH3P2 in complex with Cbl and Src.
In this report, we describe SH3P2, an SH3-domain containing protein, as a novel Cbl-interacting molecule that is a substrate of tyrosine kinase Src. We identified a specific polyproline motif of Cbl responsible for binding of SH3P2 and Src, and observed mutual sequestration of Src and SH3P2 from monomer Cbl molecules. In adherent cells, SH3P2 associated with Cbl and fibrilar actin and was localized at focal contacts in fibroblasts as well as at the apical part of podosome rings in differentiated osteoclasts. Our data implicate that SH3P2, a novel component of adhesion sites, is involved in Cbl and Src-mediated pathways.
Szymkiewicz
Iwona
I
Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany.
Destaing
Olivier
O
Jurdic
Pierre
P
Dikic
Ivan
I
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D022001:Focal Adhesions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D050722:Oncogene Protein v-cbl; D010010:Osteoclasts / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D000199:Actins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D050722:Oncogene Protein v-cbl; D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; C408994:osteoclast stimulating factor; D019000:Phosphotyrosine; C011083:polyproline; D014443:Tyrosine; D019061:src-Family Kinases