INPP4B Antibody [H1L5] Datasheet

Biological Description

Specificity	INPP4B Antibody [H1L5] detects endogenous levels of total INPP4B protein.
Background	INPP4B, or inositol polyphosphate-4-phosphatase type II, is a lipid phosphatase that modulates phosphoinositide signaling by hydrolyzing the 4-phosphate from phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), generating PI(3)P. It is expressed in the cytoplasm of nonproliferative, estrogen receptor-positive mammary epithelial cells, where it maintains low basal Akt phosphorylation under serum-starved conditions and limits EGF-stimulated Akt activation at Ser473 and Thr308 in breast cancer cells. By dephosphorylating PI(3,4)P2, INPP4B reduces the availability of this lipid for pleckstrin homology domain binding by Akt, thereby attenuating PI3K/Akt pathway signaling that promotes cell proliferation, anchorage-independent growth, and xenograft tumor formation in ER-positive models like MCF-7. In PTEN-null triple-negative breast cancer cells, INPP4B depletion paradoxically lowers basal pAkt and proliferation while increasing sensitivity to PI3Kα and PI3Kβ inhibitors, whereas overexpression confers resistance in a phosphatase-dependent manner, suggesting that PI(3,4)P2 accumulation inhibits further PI3K activity as a feedback mechanism. Reconstitution of INPP4B in ER-negative, INPP4B-null MDA-MB-231 cells suppresses EGF-dependent Akt phosphorylation and soft agar colony formation. INPP4B acts independently of INPP4A, has cytoplasmic localization distinct from PTEN, and its protein loss can occur via mechanisms beyond gene deletion, such as hypermethylation. INPP4B is predominantly expressed in luminal A breast cancers but is absent in 80-88% of aggressive basal-like subtypes, correlating with high grade, large tumor size, CK5/6 positivity, elevated Ki-67 and cyclin E1, reduced p27, and frequent PTEN loss, without being mutually exclusive to PIK3CA alterations.

Specificity

INPP4B Antibody [H1L5] detects endogenous levels of total INPP4B protein.

Background

INPP4B, or inositol polyphosphate-4-phosphatase type II, is a lipid phosphatase that modulates phosphoinositide signaling by hydrolyzing the 4-phosphate from phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), generating PI(3)P. It is expressed in the cytoplasm of nonproliferative, estrogen receptor-positive mammary epithelial cells, where it maintains low basal Akt phosphorylation under serum-starved conditions and limits EGF-stimulated Akt activation at Ser473 and Thr308 in breast cancer cells. By dephosphorylating PI(3,4)P2, INPP4B reduces the availability of this lipid for pleckstrin homology domain binding by Akt, thereby attenuating PI3K/Akt pathway signaling that promotes cell proliferation, anchorage-independent growth, and xenograft tumor formation in ER-positive models like MCF-7. In PTEN-null triple-negative breast cancer cells, INPP4B depletion paradoxically lowers basal pAkt and proliferation while increasing sensitivity to PI3Kα and PI3Kβ inhibitors, whereas overexpression confers resistance in a phosphatase-dependent manner, suggesting that PI(3,4)P2 accumulation inhibits further PI3K activity as a feedback mechanism. Reconstitution of INPP4B in ER-negative, INPP4B-null MDA-MB-231 cells suppresses EGF-dependent Akt phosphorylation and soft agar colony formation. INPP4B acts independently of INPP4A, has cytoplasmic localization distinct from PTEN, and its protein loss can occur via mechanisms beyond gene deletion, such as hypermethylation. INPP4B is predominantly expressed in luminal A breast cancers but is absent in 80-88% of aggressive basal-like subtypes, correlating with high grade, large tumor size, CK5/6 positivity, elevated Ki-67 and cyclin E1, reduced p27, and frequent PTEN loss, without being mutually exclusive to PIK3CA alterations.

Usage Information

Application

WB, IHC, IF, FCM

Dilution

WB	IHC	IF	FCM
1:1000 - 1:5000	1:50	1:50	1:100

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

105 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/28196852/
https://pubmed.ncbi.nlm.nih.gov/21127264/

INPP4B Antibody [H1L5]

Biological Description

Usage Information

References

Application Data