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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The integrin family of heterodimeric cell surface receptors play critical roles in multiple biological processes by mediating cellular adhesion to the extracellular matrix (ECM). Adhesion triggers intracellular signaling cascades, including tyrosine phosphorylation and elevation of [Ca2+]i. The Focal Adhesion Kinase (FAK or pp125FAK), a protein tyrosine kinase that colocalizes with integrins in cellular focal adhesions, is a prime candidate for a mediator of integrin signaling events. Here we report an analysis of the domain structure of FAK in which we have identified a contiguous stretch of 159 amino acids within the COOH terminus essential for correct subcellular localization. When placed in the context of an unrelated cytosolic protein, this Focal Adhesion Targeting (FAT) sequence functions to efficiently mediate the focal adhesion localization of this fusion protein. Furthermore, this analysis suggests that pp125FAK cannot be activated oncogenically by mutation. This result could be explained if pp125FK either exhibits a narrow substrate specificity or is diametrically opposed by cellular phosphatases or other cellular processes.
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PMID:Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. 822 54

Extracellular matrix molecules and their receptors are important regulators of cell movement, adhesion and cytoskeletal organization. Adhesion molecules can also serve to mediate signal transduction and can influence, and sometimes direct, the events required for tumorigenesis. The extracellular matrix molecule, hyaluronan and its receptors have been implicated in transformation and metastasis, in particular the processes of tumor cell motility and invasion. RHAMM (receptor for hyaluronan mediated motility) is required for the cell locomotion of ras-transformed fibrosarcoma cells, cytokine stimulated fibrobasts and T lymphocytes, malignant B cells, and breast carcinoma cells. HA:RHAMM interactions promote cell locomotion via a protein tyrosine kinase signal transduction pathway that targets focal adhesions. The tyrosine kinase pp60c-src is associated with RHAMM in cells and is required for RHAMM mediated cell motility. It is possible that a RHAMM/src pathway induces focal adhesions to signal the cytoskeletal changes required for elevated cell motility seen in tumor progression, invasion and metastasis.
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PMID:Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. 875 Jan 88

Focal Adhesion Kinase (FAK) is a protein tyrosine kinase, localised in the focal adhesions, which, upon activation interacts with Src, another tyrosine kinase, regulating several cellular signalling pathways. Both enzymes have been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK and Src expression in cases of endometrial adenocarcinoma. The total (t) and the activated, phosphorylated (p) forms of FAK and Src proteins were assessed immunohistochemically in tumour specimens obtained from 43 endometrial adenocarcinoma patients and were statistically analyzed in relation to various clinicopathological parameters and tumour proliferative capacity, reflected by Ki-67 labelling index. t-FAK positivity was significantly correlated with FIGO disease stage (p = 0.031), and t-FAK overexpression with patients' age (p = 0.015). No statistically significant correlation was identified between t-FAK staining intensity, t-Src positivity, overexpression or staining intensity and any of the clinicopathological parameters tested. No significant correlation was found between neither the positivity nor the intensity of staining of either p-FAk or p-Src with any of the parameters under study. Nonetheless, important, but non-significant, trends were identified between t-FAK staining intensity, t-Src positivity and overexpression and patients' survival (log rank, p = 0.122, p = 0.090 and p = 0.057 respectively). Similarly, p-FAK and p-Src staining characteristics seemed to correlate, even though non-significantly, with patients' survival (log rank, p = 0.051 and p = 0.070 for p-FAK and p-Src expression, respectively; log rank, p = 0.134 and p = 0.110 for p-FAK and p-Src staining intensity, respectively). These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress and render further research in this field a necessity.
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PMID:Expression and clinical significance of FAK and Src proteins in human endometrial adenocarcinoma. 2105 27