Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V.
The diverse cytoplasmic domain sequences within the various integrin subunits are critical for integrin-mediated signaling into the cell (outside-in signaling) and for activation of ligand binding affinity (inside-out signaling). Here we introduce an approach based on phage display technology to identify molecules that specifically interact with the cytoplasmic domain of the beta 5 integrin subunit. We show that a peptide selected for binding specifically to the beta 5 cytoplasmic domain (VVISYSMPD) induces apoptosis upon internalization. The cell death process induced by VVISYSMPD is sensitive to modulation by growth factors and by protein kinase C (PKC), and it cannot be triggered in beta 5 null cells. Finally, we show that the VVISYSMPD peptide is a mimic of annexin V. Our results suggest a functional link between the alpha v beta 5 integrin, annexin V, and programmed cell death. We propose the term "endothanatos" to designate this phenomenon.
Cardó-Vila
Marina
M
M.D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Arap
Wadih
W
Pasqualini
Renata
R
D000595:Amino Acid Sequence / Q000235:genetics; D017304:Annexin A5 / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D005822:Genetic Vectors; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018716:Molecular Mimicry / Q000502:physiology; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D017304:Annexin A5; D006133:Growth Substances; D016023:Integrins; D010455:Peptides; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D011493:Protein Kinase C