Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase

M Camps, A Nichols, C Gillieron, B Antonsson, M Muda… - Science, 1998 - science.org
M Camps, A Nichols, C Gillieron, B Antonsson, M Muda, C Chabert, U Boschert, S Arkinstall
Science, 1998science.org
MAP kinase phosphatase–3 (MKP-3) dephosphorylates phosphotyrosine and
phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP)
kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was
independent of protein kinase activity and required binding of ERK2 to the noncatalytic
amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N
nor c-Jun amino-terminal kinase–stress-activated protein kinase (JNK/SAPK) or p38 MAP …
MAP kinase phosphatase–3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N nor c-Jun amino-terminal kinase–stress-activated protein kinase (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation. These kinases were also resistant to enzymatic inactivation by MKP-3. Another homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2, JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems.
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