Molecular cloning and characterization of a novel cbl-family gene, cbl-c.
We have cloned a novel gene, cbl-c, of mammalian cbl-family. The cbl-c gene is predicted to encode a protein of 52 kDa that has a phosphotyrosine-binding domain, a RING finger and a proline-rich region. Cbl-c shows 50% homology to the amino-terminal sequences of Cbl and Cbl-b, but a sequence corresponding to the carboxy-terminal half of Cbl and Cbl-b is largely missing in Cbl-c. The expression of cbl-c mRNA is distinct from that of cbl and cbl-b mRNAs, being high in the colon and small intestine, but undetectable in brain and lymphoid tissues. The cbl-c gene is mapped in 19q13.2-13.3. Finally, the 52 kDa Cbl-c protein binds to the EGF receptor and Fyn tyrosine kinase. We conclude that Cbl-c is a novel Cbl-family adaptor protein that would regulate intracellular signaling mediated by various tyrosine kinases.
Kim
M
M
Department of Oncology, The Institute of Medical Science, The University of Tokyo, Japan.
Tezuka
T
T
Suziki
Y
Y
Sugano
S
S
Hirai
M
M
Yamamoto
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases
D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C067419:CBL protein, human