Submitted December 3, 2007
Accepted June 26, 2008
Functional Analysis of the cytoplasmic domain of the integrin 
1 subunit in endothelial cells
Tristin D Abair, Nada Bulus, Corina Borza, Munirathinam Sundaramoorthy, Roy Zent, and Ambra Pozzi*
Department of Cancer Biology, Vanderbilt University, Nashville, TN, United States
Department of Medicine, Vanderbilt University, Nashville, TN, United States
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States
Departments of Medicine, Veterans Affairs Hospital, Nashville, TN, United States
* Corresponding author; email: ambra.pozzi{at}vanderbilt.edu.
Integrin 
1
1, the major collagen type IV receptor, is expressed by endothelial cells and plays a role in both physiological and pathological angiogenesis. As the molecular mechanisms whereby this collagen IV receptor mediates endothelial cell functions are poorly understood,truncation and point mutants of the integrin 1 subunit cytoplasmic tail (a.a. 1137-1151) were generated and expressed into 1-null endothelial cells. We show that 1-null endothelial cells expressing the 1 subunit which lacks the entire cytoplasmic tail (mutant 1-1136) or all the amino acids distal to the highly conserved GFFKR motif (mutant 1-1143) have a similar phenotype to parental 1-null cells. Pro1144 and Leu1145 were shown to be necessary for 11-mediated endothelial cell proliferation; Lys1146 for adhesion, migration, and tubulogenesis and Lys1147 for tubulogenesis. Integrin 11-dependent endothelial cell proliferation is primarily mediated by ERK activation, while migration and tubulogenesis require both p38 MAPK and PI3K/Akt activation. Thus, distinct amino acids distal to the GFFKR motif of the 1 integrin cytoplasmic tail mediate activation of selective downstream signaling pathways and specific endothelial cell functions.
