What question did this study set out to answer?

To identify and characterize novel splice variants of the p85alpha regulatory subunit of PI 3-kinase that interact with insulin receptor substrate 1.

May 1, 1996Molecular and Cellular BiologyOpen Access

Insulin Receptor Substrate 1 Binds Two Novel Splice Variants of the Regulatory Subunit of Phosphatidylinositol 3-Kinase in Muscle and Brain

View Full Paper

Ask AI

Bookmark

Authors

DADavid A. AntonettiUniversity of Michigan PAPetra AlgenstaedtUniversität Hamburg CKC. Ronald KahnJoslin Diabetes Center

Discussion

Member takes

Implication

Molecular screening reveals two novel p85alpha splice variants in muscle and brain, highlighting distinct tissue-specific insulin and metabolic signaling mechanisms.

Key Points

To identify and characterize novel splice variants of the p85alpha regulatory subunit of PI 3-kinase that interact with insulin receptor substrate 1.
Screened a human skeletal muscle cDNA library using phosphorylated baculovirus-produced human insulin receptor substrate 1 (IRS-1).
Evaluated mRNA and protein expression patterns across tissues using Northern blot and Western blot analyses with specific antibodies.
Assessed protein-protein interactions between the splice variants, the p110 catalytic subunit, and IRS-1 via coprecipitation assays.
Identified p85/AS53 (~53 kDa), which replaces the BCR and SH3 domains with a unique 34-amino-acid N-terminus, and a second variant containing a 24-nucleotide insert near Ser-608.
Detected approximately 7-fold higher protein expression of p85/AS53 than standard p85 in skeletal muscle, with restricted expression primarily in skeletal muscle and brain.
Demonstrated that both p85 and p85/AS53 bind the p110 catalytic subunit, whereas full-length p85alpha exhibits preferential binding to IRS-1 following insulin stimulation.

Cite This Study

Antonetti et al. (1996) studied this question.

synapsesocial.com/papers/6a787af42e130d02afed2acb https://doi.org/10.1128/mcb.16.5.2195

View Full Paper

Ask AI

Bookmark

Implication

Molecular screening reveals two novel p85alpha splice variants in muscle and brain, highlighting distinct tissue-specific insulin and metabolic signaling mechanisms.

Insulin Receptor Substrate 1 Binds Two Novel Splice Variants of the Regulatory Subunit of Phosphatidylinositol 3-Kinase in Muscle and Brain

Discussion

Member takes

Implication

Key Points

Cite This Study

Insulin Receptor Substrate 1 Binds Two Novel Splice Variants of the Regulatory Subunit of Phosphatidylinositol 3-Kinase in Muscle and Brain

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider