DUSP16/MKP7 Antibody (Rabbit mAb) [J2N13] Datasheet

Biological Description

Specificity	DUSP16/MKP7 Antibody (Rabbit mAb) [J2N13] detects endogenous levels of total DUSP16/MKP7 proteins.
Background	DUSP16 (MKP-7) is a dual-specificity mitogen-activated protein kinase phosphatase that dephosphorylates both the threonine and tyrosine residues within the activation loop of its MAPK substrates, with substantially greater inhibitory activity toward JNK than toward p38 and comparatively little effect on ERK, distinguishing its substrate preference from other MKP family members. Structural and mutational analysis identifies a tyrosine residue, Y271, located outside the catalytic active site itself, as an allosteric regulatory position analogous to a previously characterized site in the related phosphatase MKP5; mutating this residue substantially reduces MKP7's catalytic activity toward its MAPK substrates and, correspondingly, reduces the binding efficiency between MKP7 and both p38 and JNK1/2, indicating that engagement of MAPK substrates at this allosteric site is a prerequisite step that occurs before the substrate can access MKP7's catalytic center for dephosphorylation. Cells expressing MKP7 Y271 mutants accumulate substantially more phosphorylated, nuclear p38 and JNK compared with cells expressing wild-type MKP7, which instead sequesters these MAPKs in the cytoplasm, showing that this single allosteric site controls both MKP7's catalytic dephosphorylation activity and its capacity to compartmentalize its MAPK substrates away from the nucleus. Functionally, overexpressing DUSP16 in BCR-ABL-transformed fibroblasts reduces their transforming capacity both in culture and in animal models specifically by downregulating BCR-ABL-induced JNK activation, while in a separate cellular context, DUSP16 overexpression instead increases resistance to apoptosis, together indicating that DUSP16's functional consequence, tumor-suppressive or anti-apoptotic, depends on the specific cellular and signaling context in which JNK activity is being restrained, mirroring the well-established dual, context-dependent role that JNK itself plays in driving either cell death or survival. Because no inactivating DUSP16 mutations are found in leukemia patients despite reduced gene dosage in some cases, DUSP16 is proposed to act as a haploinsufficient rather than a classically two-hit-inactivated tumor suppressor, with reduced DUSP16 expression, rather than mutation, more broadly implicated across multiple cancer types through effects on MAPK-driven proliferation and mitochondrial apoptotic signaling.

Specificity

DUSP16/MKP7 Antibody (Rabbit mAb) [J2N13] detects endogenous levels of total DUSP16/MKP7 proteins.

Background

DUSP16 (MKP-7) is a dual-specificity mitogen-activated protein kinase phosphatase that dephosphorylates both the threonine and tyrosine residues within the activation loop of its MAPK substrates, with substantially greater inhibitory activity toward JNK than toward p38 and comparatively little effect on ERK, distinguishing its substrate preference from other MKP family members. Structural and mutational analysis identifies a tyrosine residue, Y271, located outside the catalytic active site itself, as an allosteric regulatory position analogous to a previously characterized site in the related phosphatase MKP5; mutating this residue substantially reduces MKP7's catalytic activity toward its MAPK substrates and, correspondingly, reduces the binding efficiency between MKP7 and both p38 and JNK1/2, indicating that engagement of MAPK substrates at this allosteric site is a prerequisite step that occurs before the substrate can access MKP7's catalytic center for dephosphorylation. Cells expressing MKP7 Y271 mutants accumulate substantially more phosphorylated, nuclear p38 and JNK compared with cells expressing wild-type MKP7, which instead sequesters these MAPKs in the cytoplasm, showing that this single allosteric site controls both MKP7's catalytic dephosphorylation activity and its capacity to compartmentalize its MAPK substrates away from the nucleus. Functionally, overexpressing DUSP16 in BCR-ABL-transformed fibroblasts reduces their transforming capacity both in culture and in animal models specifically by downregulating BCR-ABL-induced JNK activation, while in a separate cellular context, DUSP16 overexpression instead increases resistance to apoptosis, together indicating that DUSP16's functional consequence, tumor-suppressive or anti-apoptotic, depends on the specific cellular and signaling context in which JNK activity is being restrained, mirroring the well-established dual, context-dependent role that JNK itself plays in driving either cell death or survival. Because no inactivating DUSP16 mutations are found in leukemia patients despite reduced gene dosage in some cases, DUSP16 is proposed to act as a haploinsufficient rather than a classically two-hit-inactivated tumor suppressor, with reduced DUSP16 expression, rather than mutation, more broadly implicated across multiple cancer types through effects on MAPK-driven proliferation and mitochondrial apoptotic signaling.

Usage Information

Application

WB

Dilution

WB

1:1000

Reactivity

Human, Mouse, Rat, Monkey

Source

Rabbit Monoclonal Antibody

MW

73 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/36272649/
https://pubmed.ncbi.nlm.nih.gov/14586399/

DUSP16/MKP7 Antibody (Rabbit mAb) [J2N13]

Biological Description

Usage Information

References

Application Data