Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases.
The Src family of protein tyrosine kinases (Src-PTKs) is important in the regulation of growth and differentiation of eukaryotic cells. The activity of Src-PTKs in cells of different types is negatively controlled by Csk, which specifically phosphorylates a conserved regulatory tyrosine residue at the carboxy-terminal tail of the Src-PTKs. Csk is mainly cytoplasmic and Src-PTKs are predominantly membrane-associated. This raises a question about the mechanism of interaction between these enzymes. Here we present Cbp--a transmembrane phosphoprotein that is ubiquitously expressed and binds specifically to the SH2 domain of Csk. Cbp is involved in the membrane localization of Csk and in the Csk-mediated inhibition of c-Src. In the plasma membrane Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane domain, which is important in receptor-mediated signalling. These findings reveal Cbp as a new component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs.
Kawabuchi
M
M
Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Japan.
Satomi
Y
Y
Takao
T
T
Shimonishi
Y
Y
Nada
S
S
Nagai
K
K
Tarakhovsky
A
A
Okada
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004789:Enzyme Activation; D020536:Enzyme Activators; D004926:Escherichia coli; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
D018076:DNA, Complementary; D020536:Enzyme Activators; D008565:Membrane Proteins; C408142:Pag1 protein, rat; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D019061:src-Family Kinases