Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent genetic studies have shown that Apert's syndrome results from mutations of the fibroblast growth factor (FGF) receptor 2 gene. We were interested in investigating the expression of FGF receptor 2 at the tissue level in children with Apert's syndrome. We studied FGF receptor activity in cranial sutures of children with Apert's syndrome and nonsyndromic, isolated craniosynostosis. Fourteen children between the ages of 6 months and 12 months were studied. Five of these children had Apert's syndrome with coronal suture stenosis. Nine children had an isolated, nonsyndromic coronal stenosis. Stenosed and nonstenosed cranial sutures were removed at the time of cranioplasty, fixed, decalcified, and paraffinized. Immunohistochemistry was performed with labeled, specific anti-FGR receptor 2 antibodies. We found lower levels of FGF receptor 2 staining in both stenosed and unstenosed sutures of children with Apert's syndrome compared with those from children with a nonsyndromic suture stenosis. Furthermore, fused sutures from children with Apert's syndrome demonstrated lower levels of FGF receptor 2 staining than unfused sutures from the same sample. The findings suggest that Apert's syndrome correlates with low FGF receptor 2 activity in cranial sutures. These results are consistent with and similar to our findings in Crouzon's syndrome, and support genetic studies showing localized mutational changes occurring at the FGF receptor 2 gene for both Apert's and Crouzon's syndromes. Furthermore, the findings suggest the possibility that variable expression of FGF receptor 2 occurs at the tissue level in patients with Apert's syndrome.
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PMID:Apert's syndrome correlates with low fibroblast growth factor receptor activity in stenosed cranial sutures. 955 76

Distraction osteogenesis (DO) permits gradual lengthening of the craniofacial skeleton. With the advent of new internal devices, monobloc (M) and facial bipartition (FB) DO are feasible. The rationale behind M and FB distraction is (1) gradual advancement of the M segment is not associated with a substantial retrofrontal dead space; (2) because 5 to 7 days elapse prior to distraction, the nasofrontal opening, in theory, is allowed to remucosalize; (3) gradual expansion of the soft tissues takes advantage of skin creep, potentially limiting relapse; (4) the procedure appears to be less invasive with decreased blood loss and operative time, enabling its use in infants; (5) overdistraction may eliminate or reduce the frequency of subsequent procedures; and (6) the procedure may be combined with FB and skull vault remodeling to provide excellent results in more complex craniofacial dysostosis problems. Five children underwent M advancement (N = 3) and M with FB (N = 2) at 9 months to 5 years of age to correct functional abnormalities such as corneal exposure, increased intracranial pressure, and apnea, as well as severe craniofacial disfigurement. Each patient underwent from 22 to 30 mm of distraction with the Modular Internal Distraction (MID) system, developed by the first author (SRC). There was one infection late in the series along the DO cable track. There were no cases of epidural abscess. In conclusion, MDO, with and without FB, appears to be a safe and effective technique for transcranial frontofacial advancement. The morbidity of the procedure appears to be less than that of conventional M advancement.
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PMID:Monobloc and facial bipartition distraction with internal devices. 1053 Feb 35

Skeletal development requires the correct balance of osteoblast proliferation, survival, and differentiation which is modulated by a network of signaling pathways and transcription factors. We have examined the role of the AKT (PKB), and ERK1/2 signaling pathways in the osteoblast response to FGFs, which inhibit differentiation, and to IGF-1 and Wnt signaling, which promote it. Using osteoblastic cell lines as well as primary calvarial osteoblasts, we show that ERK1/2 and AKT have distinct effects in FGF-induced osteoblast proliferation and differentiation. ERK1/2 is a primary mediator of FGF-induced proliferation, but also contributes to osteoblast differentiation, while AKT is important for osteoblast survival. Signaling by IGF-1, that promotes osteoblast differentiation, strongly activates AKT and weakly ERK1/2, while the opposite results are obtained with FGF, which inhibits differentiation. By introducing a constitutively active form of AKT, we found that increased AKT activity drives osteoblasts to differentiation. Increasing the AKT signal in osteoblasts that harbor FGFR2 activating mutations, found in Crouzon (342Y) and Apert (S22W) syndromes, is also able to drive differentiation in these cells, that normally fail to differentiate. Wnt signals, that promotes differentiation, also induce AKT phosphorylation, and cells expressing active AKT have increased levels of stabilized beta-catenin, a central molecule in Wnt signaling. Our results indicate that the relative strengths of ERK and AKT signaling pathways determine whether osteoblasts are driven into proliferation or differentiation, and that the effects of AKT may be due, in part, to synergy with the Wnt pathway as well as with the Runx2 transcription factor.
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PMID:Osteoblast proliferation or differentiation is regulated by relative strengths of opposing signaling pathways. 1796 May 91