Molecular cloning of actin filament-associated protein: a putative adaptor in stretch-induced Src activation.
Mechanical stretch-induced activation of c-Src is an important step for signal transduction of stretch-induced fetal rat lung cell proliferation. This process appears to be mediated through actin filament-associated protein (AFAP), encoded by a gene originally cloned from the chicken. In the present study, we cloned the rat AFAP gene from fetal rat lungs. Its mRNA and protein are differentially expressed among various tissues. The protein is colocalized with actin filaments in fetal rat lung epithelial cells and fibroblasts. Mechanical stretch increased tyrosine phosphorylation of rat AFAP and its binding to c-Src within the initial several minutes. Src SH2 and SH3 binding motifs are highly conserved in the AFAP proteins (from chicken, rat to human). On the basis of the molecular structure of AFAP protein, we speculate that it is an adaptor in mechanical stretch-induced activation of c-Src. A novel model of mechanoreception is proposed.
Thoracic Surgery Research Laboratory, Division of Cellular and Molecular Biology, University Health Network Toronto General Research Institute and Department of Surgery, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
Monika
M
Lodyga
Xiao-Hui
XH
Bai
Eric
E
Mourgeon
Bing
B
Han
Shaf
S
Keshavjee
Mingyao
M
Liu
D000199:Actins / Q000502:physiology; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D003001:Cloning, Molecular; D005333:Fetus / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008168:Lung / Q000196:embryology; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D051381:Rats / Q000196:embryology / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013314:Stress, Mechanical; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism
C084510:AFAP 110; D000199:Actins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)