In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines.
Integrins are heterodimeric adhesion receptors associated with bidirectional signaling. In vitro studies support a role for the binding of evolutionarily conserved tyrosine motifs (NPxY) in the beta integrin cytoplasmic tail to phosphotyrosine-binding (PTB) domain-containing proteins, an interaction proposed to be dynamically regulated by tyrosine phosphorylation. Here we show that replacement of both beta1 integrin cytoplasmic tyrosines with alanines, resulting in the loss of all PTB domain interaction, causes complete loss of beta1 integrin function in vivo. In contrast, replacement of beta1 integrin cytoplasmic tyrosines with phenylalanines, a mutation that prevents tyrosine phosphorylation, conserves in vivo integrin function. These results have important implications for the molecular mechanism and regulation of integrin function.
Chen
Hong
H
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Zou
Zhiying
Z
Sarratt
Kendra L
KL
Zhou
Diane
D
Zhang
MaoZhen
M
Sebzda
Eric
E
Hammer
Daniel A
DA
Kahn
Mark L
ML
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D019012:Integrin beta1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D014443:Tyrosine / Q000502:physiology*
D017931:DNA Primers; D019012:Integrin beta1; D014443:Tyrosine