Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene.
We have cloned a new gene, cbl-b, with homology to the c-cbl proto-oncogene. A large protein is predicted (approx. MW 108,000) that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a putative leucine zipper. There is striking nucleotide and amino acid homology to the c-cbl proto-oncogene most notably in the structural motifs described above. Cbl-b is expressed in normal and malignant mammary epithelial cells, in a variety of normal tissues, and in hematopoietic tissue and cell lines. Cbl-b expressions is up-regulated with macrophage/monocyte differentiation of the HL60 and U937 cell lines. There is direct association of the cbl-b protein with the Src Homology 3 domains of several proteins including signaling, cytoskeletal and adaptor proteins. Our data suggest that cbl-b encodes a protein which can interact with signal transduction proteins to regulate their function or to be regulated by them. Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction.
Keane
M M
MM
National Cancer Institute-Navy Medical Oncology Branch, Bethesda Naval Hospital, Maryland 20889, USA.
Rivero-Lezcano
O M
OM
Mitchell
J A
JA
Robbins
K C
KC
Lipkowitz
S
S
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D018076:DNA, Complementary; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins