The ups and downs of SRC regulation: tumor suppression by Cbp.
Tight control of the tyrosine kinase activity of c-Src is critical for regulating its oncogenic potential. In a recent issue of Molecular Cell, Oneyama et al. (2008a) report that the membrane-bound adaptor protein Cbp (also known as PAG) can suppress c-Src-mediated cell transformation and tumorigenesis by binding and sequestering c-Src within lipid rafts. Cbp is also a raft-associated binding partner for Csk, a negative regulator of c-Src. However, the authors show that Cbp-mediated Src suppression is Csk independent. These findings suggest that Cbp is a tumor suppressor whose expression is downregulated during Src-driven cancer progression.
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. m-resh@ski.mskcc.org
Marilyn D
MD
Resh
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human