| First Author | Smith DP | Year | 2001 |
| Journal | Hum Mol Genet | Volume | 10 |
| Issue | 25 | Pages | 2869-77 |
| PubMed ID | 11741830 | Mgi Jnum | J:155212 |
| Mgi Id | MGI:4412462 | Doi | 10.1093/hmg/10.25.2869 |
| Citation | Smith DP, et al. (2001) LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Hum Mol Genet 10(25):2869-77 |
| abstractText | LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a protein of 121 kDa. LIP1 appears to be a cytoplasmically located protein whereas we and others have shown previously that LKB1 is predominantly nuclear, with only a small proportion of cells showing strong cytoplasmic expression. However, when LKB1 and LIP1 are co-expressed, the proportion of cytoplasmic LKB1 dramatically increases, suggesting that LIP1 may regulate LKB1 function by controlling its subcellular localization. Ectopic expression of both LKB1 and LIP1 in Xenopus embryos induces a secondary body axis, providing further evidence for a functional link between the two proteins. This phenotype resembles the effects of ectopic expression of TGFbeta superfamily members and their downstream effectors. A possible role for LIP1 and LKB1 in TGFbeta signalling is supported by the observation that LIP1 interacts with the TGFbeta-regulated transcription factor SMAD4, forming a LKB1-LIP1-SMAD4 ternary complex. SMAD4 mutations give rise to juvenile polyposis syndrome, which is clinically similar to PJS. Our data suggest an unsuspected mechanistic link between these two syndromes. |
