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Enzyme
Compound
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Gene/Protein
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Target Concepts:
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Query: UNIPROT:P04626 (
erbB-2
)
5,251
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A growth factor-stimulated protein kinase activity that phosphorylates the
epidermal growth factor (EGF) receptor
at Thr669 has been described (Countaway, J. L., Northwood, I. C., and Davis, R. J. (1989) J. Biol. Chem. 264, 10828-10835). Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the
microtubule-associated protein 2
(
MAP2
) kinase. However, the second peak of activity was found to be a distinct enzyme. We present here the purification of this enzyme from human tumor KB cells by sequential ion-exchange chromatography. The isolated protein kinase was identified as a 46-kDa protein by polyacrylamide gel electrophoresis and silver staining. Gel filtration chromatography demonstrated that the enzyme was functional in a monomeric state. A kinetic analysis of the purified enzyme was performed at 22 degrees C using a synthetic peptide substrate based on the primary sequence of the EGF receptor (KREL VEPLT669PSGEAPNQALLR). The Km(app) for ATP was 40 +/- 5 microM (mean +/- S.D., n = 3). GTP was not found to be a substrate for the purified enzyme. The Km(app) for the synthetic peptide substrate was 260 +/- 40 microM (mean +/- S.D., n = 3). The Vmax(app) for the isolated protein kinase was determined to be 400-900 nmol/mg/min. The purified enzyme was designated EGF receptor Thr669 (ERT) kinase. It is likely that the
MAP2
and ERT kinases account for the phosphorylation of the EGF receptor at Thr669 observed in cultured cells. The marked stimulation of protein kinase activity caused by growth factors indicates that these enzymes may have an important function during signal transduction.
...
PMID:Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669. 165 22
We have examined the effect of tyrosine phosphorylation of
microtubule-associated protein 2
(
MAP2
) by the
epidermal growth factor (EGF) receptor
kinase on its functions. Incubation of
MAP2
with the EGF receptor in the presence of ATP resulted in a great decrease in the ability of
MAP2
to promote tubulin polymerization. Under a variety of conditions, the decrease in the ability correlated with the extent of phosphorylation of
MAP2
. Furthermore, another function of
MAP2
, the actin filament cross-linking activity, was also inactivated by the incubation of
MAP2
with the EGF receptor and ATP. The loss of this activity also correlated well with the extent of phosphorylation. These data indicate that tyrosine phosphorylation of
MAP2
by the EGF receptor kinase inactivates both the tubulin polymerizing activity and actin filament cross-linking activity of
MAP2
. Thus, this study has clearly shown that tyrosine phosphorylation could modify the function of a cytoskeletal protein.
...
PMID:Tyrosine phosphorylation by the epidermal growth factor receptor kinase induces functional alterations in microtubule-associated protein 2. 282 82
