RGD Reference Report - Insulin-like growth factors require phosphatidylinositol 3-kinase to signal myogenesis: dominant negative p85 expression blocks differentiation of L6E9 muscle cells. - Rat Genome Database

RGD Reference Report - Insulin-like growth factors require phosphatidylinositol 3-kinase to signal myogenesis: dominant negative p85 expression blocks differentiation of L6E9 muscle cells. - Rat Genome Database

Submit Data | Help | Video Tutorials | News | Publications | Download | REST API | Citing RGD | Contact

General

Insulin-like growth factors require phosphatidylinositol 3-kinase to signal myogenesis: dominant negative p85 expression blocks differentiation of L6E9 muscle cells.
Authors:	Kaliman, P Canicio, J Shepherd, PR Beeton, CA Testar, X Palacin, M Zorzano, A
Citation:	Kaliman P, etal., Mol Endocrinol. 1998 Jan;12(1):66-77.
RGD ID:	1625263
Pubmed:	PMID:9440811 (View Abstract at PubMed)
DOI:	DOI:10.1210/mend.12.1.0047 (Journal Full-text)
Phosphatidylinositol 3 (PI 3)-kinases are potently inhibited by two structurally unrelated membrane-permeant reagents: wortmannin and LY294002. By using these two inhibitors we first suggested the involvement of a PI 3-kinase activity in muscle cell differentiation. However, several reports have described that these compounds are not as selective for PI 3-kinase activity as assumed. Here we show that LY294002 blocks the myogenic pathway elicited by insulin-like growth factors (IGFs), and we confirm the specific involvement of PI 3-kinase in IGF-induced myogenesis by overexpressing in L6E9 myoblasts a dominant negative p85 PI 3-kinase-regulatory subunit (L6E9-delta p85). IGF-I, des(1-3)IGF-I, or IGF-II induced L6E9 skeletal muscle cell differentiation as measured by myotube formation, myogenin gene expression, and GLUT4 glucose carrier induction. The addition of LY294002 to the differentiation medium totally inhibited these IGF-induced myogenic events without altering the expression of a non-muscle-specific protein, beta1-integrin. Independent clones of L6E9 myoblasts expressing a dominant negative mutant of the p85-regulatory subunit (delta p85) showed markedly impaired glucose transport activity and formation of p85/p110 complexes in response to insulin, consistent with the inhibition of PI 3-kinase activity. IGF-induced myogenic parameters in L6E9-delta p85 cells, ie. cell fusion and myogenin gene and GLUT4 expression, were severely impaired compared with parental cells or L6E9 cells expressing wild-type p85. In all, data presented here indicate that PI 3-kinase is essential for IGF-induced muscle differentiation and that the specific PI 3-kinase subclass involved in myogenesis is the heterodimeric p85-p110 enzyme.

Gene Ontology Annotations Click to see Annotation Detail View

Biological Process

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
glucose metabolic process		IMP		1625263		RGD
insulin-like growth factor receptor signaling pathway		IMP		1625263		RGD
positive regulation of myoblast differentiation		IMP		1625263		RGD

Objects Annotated

Genes (Rattus norvegicus)

Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1)

Additional Information