Focal adhesion kinase is abundant in developing blood vessels and elevation of its phosphotyrosine content in vascular smooth muscle cells is a rapid response to angiotensin II.
Focal adhesion kinase (FAK) is a structurally unique nonreceptor protein-tyrosine kinase that localizes to focal adhesion plaques. Regulation of its activity has been implicated in diverse signaling pathways, including those mediated by extracellular matrix/integrin interactions, G-protein coupled receptors for mitogenic neuropeptides, and certain oncogene products. To gain evidence for specific processes in which FAK may be involved in vivo, a study was initiated to determine its expression pattern during mouse development. FAK expression was detected in early embryos and appeared to be distributed throughout all cell types at about the time of neurulation. Subsequent to neural tube closure, expression became particularly abundant in the developing vasculature. This included expression in the medial layer of arteries populated by smooth muscle cells. In vitro studies using cultured rat aortic vascular smooth muscle cells demonstrate that FAK phosphotyrosine content is dramatically elevated in response to plating cells onto the adhesive glycoprotein, fibronectin. Also, enhanced tyrosine phosphorylation of FAK is observed in these cells upon stimulation with the vasoconstrictor angiotensin II. Thus, in vascular smooth muscle cells, like fibroblasts, FAK appears to play a role in signaling mechanisms induced by extracellular matrix components as well as G-protein coupled receptor agonists. The combined results of this study suggest that signaling through FAK may play an important role in blood vessel morphogenesis and function.
Polte
T R
TR
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Naftilan
A J
AJ
Hanks
S K
SK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D000804:Angiotensin II; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse