Surfing the insulin signaling web.
The diverse biological actions of insulin and insulin-like growth factor I (IGF-I) are initiated by binding of the polypeptides to their respective cell surface tyrosine kinase receptors. These activated receptors phosphorylate a series of endogenous substrates on tyrosine, amongst which the insulin receptor substrate (IRS) proteins are the best characterized. Their phosphotyrosine-containing motifs become binding sites for Src homology 2 (SH2) domains on proteins such as SH2 domain-containing protein-tyrosine-phosphatase (SHP)-2/Syp, growth factor receptor bound-2 protein, (Grb-2), and phosphatidyl inositol 3 kinase (PI3 kinase), which participate in activation of specific signaling cascades. However, the IRS molecules are not only platforms for signaling molecules, they also orchestrate the generation of signal specificity, integration of signals induced by several extracellular stimuli, and signal termination and modulation. An extensive review is beyond the scope of the present article, which will be centered on our own contribution and reflect our biases.
Van Obberghen
E
E
Inserm U 145, IFR 50, Faculté de Médecine, Avenue de Valombrose, Nice Cedex, France. vanobbeg@unice.fr
Baron
V
V
Delahaye
L
L
Emanuelli
B
B
Filippa
N
N
Giorgetti-Peraldi
S
S
Lebrun
P
P
Mothe-Satney
I
I
Peraldi
P
P
Rocchi
S
S
Sawka-Verhelle
D
D
Tartare-Deckert
S
S
Giudicelli
J
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008894:Milk Proteins; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C098587:GAB1 protein, human; D007328:Insulin; D016023:Integrins; D008894:Milk Proteins; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1