Biomedical subjects

I Virtanen

Publications and source records attributed to I Virtanen.

At least 19 recordsLinked to original sources

PubMed1996

The immunohistochemical composition of the human corneal basement membrane.

Frozen sections of human cornea and conjunctiva were stained by immunofluorescence and immunoperoxidase methods with a panel of antibodies against various basement membrane (BM) and extracellular matrix proteins to study the composition of the human corneal BM. Laminin (Ln) immunoreactivity was detected in the BMs of the blood vessels and conjunctival, limbal, and corneal epithelia by using a polyclonal antiserum and monoclonal antibodies (MAbs) against Ln chains alpha 1, beta 1, and gamma 1, but in the cornea the reaction with MAbs against alpha 1, beta 1, and gamma 1 chains was clearly weaker than in the other BMs and in some sections totally absent. Immunoreactivity to Ln alpha 2 chain was detected only in the BM of the limbus, whereas Ln beta 2 chain was detected in the BMs of blood vessels and that of conjunctival and limbal epithelia. Ln-5 and Ln alpha 3 and beta 3 chains were seen in the BMs of the corneal, limbal, and conjunctival epithelia coaligning the integrin beta 4. Immunoreactivity for collagen type IV was lacking in the BM of the corneal epithelium, but present in the BMs of the limbal and conjunctival epithelia as well as in the vascular BM. Collagen type VII immunoreactivity was seen in the BM areas of the corneal, limbal, and conjunctival epithelia. BMs of corneal, limbal, conjunctival, and vascular epithelia expressed fibronectin (Fn), including extradomain A cellular Fn and oncofetal cellular Fn isoforms, all lacking, however, extradomain B cellular Fn. The present results give new information on the Ln chain distribution and show that the BM of the corneal epithelium differs from that of surrounding epithelia by the lack of collagen type IV.

Adolescent↗

PubMed1996

Tenascin immunoreactivity as a prognostic marker in usual interstitial pneumonia.

In this investigation, tenascin (Tn) expression was studied in 51 cases of different types of fibrotic lung disorders originating for years 1981 to 1995. Our aim was to test if accumulation of Tn at the site of lung injury in usual interstitial pneumonia (UIP) could correlate with the prognosis. Lung biopsies taken from 28 patients with UIP, six with desquamative interstitial pneumonia (DIP), six with sarcoidosis, five with extrinsic allergic bronchioloalveolitis, five with bronchiolitis obliterans organizing pneumonia (BOOP), and one with nonspecific interstitial pneumonia were studied for the expression of Tn by using an immunohistochemical technique. In addition to Tn immunohistochemistry, selected cases were also studied by immunoelectron microscopy and Western blotting. For prognostic studies in UIP the clinical follow-up information was obtained from the patient records. The expression of Tn was increased in each type of fibrosis, especially in UIP. In immunoelectron microscopy the most prominent labeling in UIP was found in association with collagen fibers and within the type 2 pneumocytes. Every studied case of UIP showed reactivity for a polypeptide of M(r) approximately equal to 200,000 by Western blotting. In patients with UIP, increased Tn expression, especially under metaplastic bronchiolar-type epithelium, was associated with a shortened survival time. Immunoelectron microscopic findings support the idea that Tn in UIP is synthesized by the regenerating epithelial rather than interstitial cells in response to pulmonary interstitial inflammation.

Adult↗

PubMed1996

Differential expression of laminins and their integrin receptors in developing and adult human lung.

Laminins (Ln) appear to play an important role in the morphogenesis of airways. We studied the expression of different laminin chains and their integrin receptors in fetal and adult lung by immunohistochemistry. Special attention was focused on the changes in the expression of these proteins during the development from the pseudoglandular (PG) and canalicular stages to adult lung, and on the possible implications of the changes for the normal lung development. The most significant changes in the expression pattern were found during the development from the PG stage to the canalicular stage. Basement membranes (BM) of both the epithelial buds and the becoming bronchi showed reactivity for Ln-alpha 1, -alpha 3, and -beta 3 chains at all stages. The alpha 2 chain was expressed only in the epithelial buds at the PG stage, and could not be found in any epithelial structures at the canalicular stage. Similarly, at the PG stage the Ln-beta 2 chain was expressed in BMs of both epithelial buds and bronchi but disappeared from the bronchial BM before the canalicular stage. Ln-beta 1 chain appeared in the bronchial BM first in the mature lung, which suggests the presence of uncharacterized Ln-beta chains earlier in development. There were considerable changes in the expression of integrins (Int) concomitantly with alterations in the composition of the BMs. At the PG stage the epithelial buds showed reactivity for Int-alpha 2 -alpha 3, and -alpha 6 subunits, but at the canalicular stage the Int-alpha 2 and -alpha 6 subunits disappeared, and only Int-alpha 3 integrin subunit was found in evolving alveolar walls; Int-alpha 6 was found in capillaries. A similar distribution of Int subunits was also found in adult alveoli. The bronchi expressed Int-alpha 2, -alpha 3, and -alpha 6 subunits at all developmental stages, but the Int-beta 4 subunit emerged first at the canalicular stage. Our results suggest that there are major changes in the expression of Ln and their Int receptors during morphogenesis of the lung, which may be important for normal development.

Adult↗

PubMed1996

Expression of megakaryocytic and erythroid properties in human leukemic cells.

Previous studies have suggested that megakaryocytes and erythrocytes may share a common precursor cell. However, studies on the commitment to erythroid and megakaryocytic lineages have been hampered by the lack of suitable human leukemic cell lines having this kind of bipotential differentiation capability. We investigated the coexpression of megakaryocytic and erythroid markers in human leukemic cell lines as well as the capability of these cells to further differentiate upon exposure to differentiation-inducing agents. We report that the JK-1 cell line, previously characterized as a typically erythroid cell line with spontaneous differentiation to red cells, actually coexpressed megakaryocytic cell surface antigens and erythroid spectrins. We also report that the JK-1 cells could be induced to differentiate along the megakaryocytic lineage by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The other cell lines studied variably expressed megakaryocytic and erythroid antigens, the DAMI and CMK cells predominantly megakaryocytic properties and the T-33 and K562 cells some erythroid markers, whereas the HEL cells expressed markers for both lineages of differentiation. Our results suggest that the JK-1 cell line represents an immature cell population that has not yet been committed to either of the two lineages of differentiation. The JK-1 cell line might provide a useful tool for further studies on the transcriptional regulation of erythroid and megakaryocytic phenotypes and for studies on the commitment to these lineages of differentiation. Our results also suggest that the leukemic cell lines show a considerable plasticity in the expression of properties normally specific for distinct lineages of differentiation.

Antigens, CD↗

PubMed1996

Alpha 6 beta 4 integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma. Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: implications for acquisition of the invading phenotype.

We studied the expression and distribution of different laminin chains, the alpha 6 beta 4 integrin and type VII collagen, i.e., components of the epithelial adhesion complex, in gastric carcinomas and in suggested preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha 6 beta 4 integrin, which is a receptor for both laminin-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastric epithelium showed a similar expression pattern of laminins and the alpha 6 beta 4 integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha 6 beta 4 integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma, and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta 4 integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma.

Antigens, Surface↗

PubMed1995

Expression of E- and N-cadherin in renal cell carcinomas, in renal cell carcinoma cell lines in vitro and in their xenografts.

E- and N-cadherins are proteins involved in intercellular adhesion and are localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules express these molecules in a distinctive pattern, the expression of N-cadherin being restricted to proximal tubules and that of E-cadherin to distal tubules and collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to originate from these tubular epithelia. To find out whether cadherins could serve as markers for a cellular origin of these tumors, we studied the expression of E- and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as did 2 of the 4 cell lines studied. The expression pattern did not correlate with the histological grade of the tumors, and even the least differentiated tumors, as well as metastases, showed expression of cadherins. Renal oncocytomas expressed E-cadherin but not N-cadherin, which is in line with previous studies that have proposed a collecting duct origin for these tumors. Papillary renal neoplasms, a separate entity usually not classified as RCC, expressed neither of the cadherins studied despite the abundant expression of beta-catenin. Our results suggest that most RCCs co-express the characteristic adhesion molecules of both proximal and distal tubules, which makes it questionable whether the origin of these tumors can be reliably located to any distinct part of the renal tubule. Our results also suggest that in RCCs the increased histological grade is not directly associated with changes in the expression of either of the cadherins, indicating other mechanisms underlying the deficient capacity to form polarized tubular structures.

Aged↗

PubMed1995

Tenascin and fibronectin isoforms in human renal cell carcinomas, renal cell carcinoma cell lines and xenografts in nude mice.

We studied the expression of tenascin (Tn) and isoforms of fibronectin (Fn) in human renal cell carcinomas (RCC) and oncocytomas, in RCC cell lines and in their s.c. implanted xenografts in nude mice. In well-differentiated RCCs and oncocytomas extra-domain A (EDA)-Fn and Tn immunoreactivities were confined to the basement membranes and blood vessels, while in less-differentiated RCCs they were also widely seen in the stroma, correlating with the morphological differentiation of the tumor. Expression of EDB-Fn and oncofetal (onc)-Fn was very scarce in most of the RCCs and oncocytomas. Western blotting results demonstrated the predominance of the M(r) 190,000 Tn subunit in most RCCs. Among the 4 RCC cell lines, 3 showed Tn in the extracellular matrix. As xenografts, they formed moderately or poorly differentiated tumors, with abundant Tn. Three of the RCC cell lines also showed secretion of EDA-Fn and 2 of them secretion of onc-Fn and EDB-Fn into the culture medium, while in xenografts there was a strong expression of all Fn isoforms. In xenografts, the expression of Tn closely recapitulated that seen in clinical tumors and in the cell lines in vitro, while the expression of Fn isoforms in cultured cells and their xenografts was highly discordant.

Animals↗

PubMed1995

Tenascin is present in human muscle spindles and neuromuscular junctions.

We used immunocytochemistry to investigate the presence of tenascin, an extracellular matrix glycoprotein with very restricted tissue distribution, in human skeletal muscle. Tenascin was found in a short segment of the muscle spindle fibres, in the equatorial region where the sensory endings are found, and in the outer layers of the spindle capsule. Tenascin was also found in the neuromuscular junctions of the extrafusal fibres. The close spatial relationship between tenascin and both sensory and motor nerve endings shown here suggests that this glycoprotein is of functional importance in adult nerve-muscle contacts in human skeletal muscle.

Adolescent↗

PubMed1995

Mutation of the cytoplasmic domain of the integrin beta 3 subunit. Differential effects on cell spreading, recruitment to adhesion plaques, endocytosis, and phagocytosis.

The cytoplasmic domain of the beta subunit of the alpha IIb beta 3 integrin is required for cell spreading on fibrinogen. Here we report that deletion of six amino acids from the COOH terminus of the beta 3 (I757TYRGT) totally abolished cell spreading and formation of adhesion plaques, whereas retaining Ile757 partially preserved these functions. We further found that substitution of Tyr747 with Ala also abolished alpha IIb beta a-mediated cell spreading. The effects of these and other mutations on additional functions of alpha IIb beta 3 were also studied. Progressive truncations of beta 3, in which stop codons were inserted at amino acid positions 759-756, caused partial defects in the recruitment of alpha IIb beta 3 to preestablished adhesion plaques and a gradual decrease in the ability of alpha IIb beta 3 to mediate internalization of fibrinogen-coated particles. The Tyr747-->Ala substitution mutant was almost totally inactive in both of these assays. Point mutations at Tyr759, and at a conserved area close to the transmembrane domain of beta 3, decreased integrin recruitment to preestablished adhesion plaques but allowed alpha IIb beta 3-mediated formation of these structures and partial cell spreading. Deletion of the cytoplasmic domain of beta 3 did not affect the constitutive endocytosis of alpha IIb beta 3.

Amino Acid Sequence↗

PubMed1995

Influence of short-term hydrostatic pressure on organization of stress fibers in cultured chondrocytes.

The present study describes changes in the organization of stress fibers that occur in articular cartilage chondrocytes subjected to hydrostatic pressure. Primary cultures of chondrocytes from bovine articular cartilage, grown on coverslips, were subjected to 5, 15, or 30 MPa hydrostatic pressure at 37 degrees C. The pressure was applied continuously or cyclically at two frequencies: 0.125 Hz (4 seconds of pressure and 4 seconds of no pressure) or 0.05 Hz (1 second of pressure and 19 seconds of no pressure) for a period of 2 hours. Control chondrocytes showed a polygonal form with prominent stress fibers extending across the cells. The exposure of cells to 30 MPa pressure caused a nearly total disappearance of stress fibers and retraction of the cells from each other. With pressure at 15 MPa or cyclic pressure, the number of cells with stress fibers was decreased. In cells subjected to 5 MPa pressure, the stress fibers resembled those in control chondrocytes. The pressure effects were reversible after 2 hours. Pressure had no effect on the staining pattern of vinculin, which suggests that microfilaments are more vulnerable to pressure than vinculin. The results indicate that cytoskeletal changes may be an integral part of the response of chondrocytes to hydrostatic pressure.

Animals↗

PubMed1995

Integrins in human anterior chamber angle.

BACKGROUND: Integrins, which are composed of an alpha and beta subunit, are capable of binding to a number of extracellular matrix proteins and, hence, affect cell adhesion and proliferation. METHODS: The distribution of the integrin beta (beta 1, beta 3-beta 5) and alpha (alpha 1-6 and alpha v) subunits in human anterior chamber angle was studied in eyes from subjects aged 9 months to 81 years using the indirect immunofluorescence technique. RESULTS: Immunoreaction for the beta 1 subunit was found throughout the trabecular meshwork (TM), in the cribriform layer, and in the endothelial lining of Schlemm's canal (SC). Labelling for the alpha 3 subunit was found in the TM and the cribriform layer only. In infant eyes the alpha 5 subunit was present in all three areas with the highest concentration in the cribriform layer, whereas no reaction was observed in adult eyes. The alpha 6 subunit was localized to the endothelium of SC only. Immunoreaction for the alpha v subunit was present in the TM and the cribriform layer of infants and young adults. CONCLUSION: The present results suggest the presence of several integrin heterodimers, acting as potential receptors for laminin, collagen, fibronectin, and vitronectin, in the anterior chamber angle.

Adolescent↗

PubMed1995

Immuno-electron-microscopic localization of types III pN-collagen and IV collagen, laminin and tenascin in developing and adult human spleen.

The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells.

Adult↗

PubMed1995

Tenascin expression in mucocutaneous diseases and related lesions of human oral mucosa.

The expression of tenascin was assessed immunohistochemically. In normal oral mucosa, immunoreactivity for tenascin was seen either as a delicate line underlining the epithelium or in the stromal papillae. In oral lichen planus, a marked enhancement of tenascin immunoreactivity in the lamina propria was associated with focal infiltrates of inflammatory cells and seemed to reflect the intensity of inflammation. In lichenoid reactions in which only a sparse inflammatory infiltrate was present a band-like tenascin reactivity was seen. Oral psoriform reactions and chronic hyperplastic candidosis showed a prominent tenascin reaction in the connective tissue papillae among infiltrates of inflammatory cells. The results show that tenascin content is increased in oral mucocutaneous diseases and related lesions and that the abundance of tenascin reflects the intensity of the inflammatory reaction.

Candidiasis, Oral↗

PubMed1995

Distribution of neurofilament proteins and peripherin in the rat pituitary gland.

The distribution of neurofilament proteins and peripherin in the pituitary gland of the rat was studied with a panel of monoclonal and polyclonal antibodies recognizing different neurofilament subunits. In the posterior lobe, a dense plexus of neurofilament- and peripherin-immunoreactive fibers was seen. In the intermediate lobe neurofilament- and peripherin-immunoreactivity was seen only in nerve fibers in the connective tissue septa, while no immunoreactivity was seen in parenchymal nerve fibers. Bilateral sympathetic ganglionectomy did not affect peripherin-immunoreactivity, indicating that the peripherin-immunoreactive fibers are of central origin. In the anterior lobe, a few solitary neurofilament- and peripherin-immunoreactive fibers were observed. Western blotting confirmed the presence of 150 kD and 200 kD neurofilament proteins in the posterior lobe. No neurofilament protein was detected in the intermediate and anterior lobes. Abundant intermediate filaments were seen with electron microscopy in the nerve fibers of the connective tissue septa in the intermediate lobe. In the parenchymal nerve fibers only microtubules were seen, indicating that the lack of neurofilament immunoreactivity is due to absence of neurofilaments.

Animals↗

PubMed1995

Early perivenular fibrogenesis--precirrhotic lesions among moderate alcohol consumers and chronic alcoholics.

Cirrhosis is believed to be preceded by "precirrhotic" lesions indicating initial fibrogenesis in the perivenular area. We investigated three previously described markers of early perivenular fibrogenesis: the thickness of the rim of the terminal hepatic venule, perivenular fibrosis and perivenular fibronectin deposition. The frequencies of these features were evaluated and compared to long-term daily alcohol intake in autopsy series of 120 males comprising abstainers, moderate alcohol consumers and chronic heavy alcohol consumers. Thickening of the rim of the terminal hepatic venule showed no correlation to the long-term daily ethanol intake. In contrast, compared to abstainers, daily alcohol intake between 40 and 80 g for an average of 25 years was associated in an increased number of subjects with perivenular fibrosis (13.3% vs 38.9%, p < 0.05), and with perivenular fibronectin deposition (13.3% vs 44.4%, p < 0.025). Similarly, daily intake exceeding 80 g was associated in an increased number of subjects with perivenular fibrosis (56.1%, p < 0.001) and with perivenular fibronectin deposition (56.1%, p < 0.001). A daily intake exceeding 80 g (110 g/d vs 240 g/d) did not, however, further increase the occurrence of these lesions. A daily intake below 40 g of absolute alcohol was not associated with signs of early perivenular fibrogenesis. In this study, the frequencies of subjects with perivenular fibrosis and perivenular fibronectin deposition correlated with the amount of daily alcohol intake. A daily intake between 40 and 80 g was associated with approximately a three-fold and a daily intake exceeding 80 g with approximately a five-fold increase in the risk of these features. This could suggest that daily intake between 40 and 80 g represents a "threshold" level, beyond which the risk of alcoholic liver fibrosis increases significantly. The majority (50-70%) of chronic heavy alcohol consumers presented signs of early perivenular fibrogenesis, whereas cirrhosis was found in only 20% of heavy consumers. This could suggest that alcohol-induced fibrotic lesions of the liver may develop in the majority of people, but factors other than cumulative alcohol consumpation may have a critical impact on the progression of early liver fibrosis to cirrhosis.

Adult↗

PubMed1995

Alpha-actinin in nemaline bodies in congenital nemaline myopathy: immunological confirmation by light and electron microscopy.

To elucidate the protein composition of the nemaline bodies present in the muscle fibres of patients with congenital nemaline myopathy (CNM), we studied muscle biopsies with monoclonal antibodies against alpha-actinin and desmin in combination with a modified Gomori trichrome method. Electron microscopy of immunolabelled resin embedded sections was used for cytochemical localisation of alpha-actinin and desmin. Light microscopy of sections immunolabelled for alpha-actinin showed a cross-striation of the muscle fibres corresponding to the Z band pattern, focal thickening of the Z bands and additional reactivity with a granular pattern corresponding to the presence of nemaline bodies. Labelling of desmin did not show a similar pattern. Electron microscopy confirmed the presence of alpha-actinin in the nemaline bodies and Z bands, whereas desmin was only found in intermediate filaments around the Z bands. Western blots showed single, sharp alpha-actinin bands indistinguishable from normal. Our results provide direct evidence for the presence of alpha-actinin in nemaline bodies and a lack of quantitative or qualitative differences between the alpha-actinin of normal and CNM muscle.

Actinin↗

PubMed1995

Lack of effect of hormonal treatment and smoking on cytokeratin expression in buccal mucosa.

Differences in cytokeratin expression of clinically normal buccal mucosa were studied in 50 healthy women by indirect immunofluorescence staining with monoclonal antibodies. The subjects were divided into four groups: control group (N = 18), smokers (N = 8), oral contraceptive users (N = 8) and smokers receiving oral contraceptives (N = 16). Our findings indicate that cytokeratin expression in noncornified stratified epithelium is not influenced by smoking or oestradiol/progesterone treatment. Only cytokeratin No. 19 showed variable patterns of expression but the differences could not be ascribed to smoking or contraceptives. Cytokeratin No. 19 gave a positive reaction in the basal and suprabasal layers in 34 subjects (68%). In 9 (18%) specimens, the staining was positive in the basal cells and showed a positive heterogeneous cytoplasmic reaction in the suprabasal cells. Interestingly, cytokeratin No. 7 was recognized in all epithelial cells except the basal cells. Our results suggest that changes in the serum oestradiol levels do not affect the cytokeratin pattern in buccal mucosa.

Adult↗

PubMed1995

Overexpressed Csk tyrosine kinase is localized in focal adhesions, causes reorganization of alpha v beta 5 integrin, and interferes with HeLa cell spreading.

The C-terminal Src kinase p50csk phosphorylates Src family tyrosine kinases and down-regulates their activity in vitro. To gain insight into the cellular functions of this potentially antioncogenic enzyme, we have overexpressed the csk cDNA by using an inducible promoter in HeLa cells. Despite some differences in basal Src activity in the clones analyzed, Src activity was not significantly suppressed, while the amount of p50csk and Csk activity increased at least 10-fold during 3 days of induction. Immunofluorescence for the induced p50csk was localized in the cytoplasm and distinctly in focal adhesions, in which the amount of phosphotyrosine containing proteins was also increased. Point and deletion mutagenesis experiments showed that localization in focal adhesions was dependent on the SH2 and SH3 domains of Csk but not on its catalytic activity. Csk formed a complex with the focal adhesion protein paxillin in cells, and its SH2 domain was shown to interact with pp125FAK and paxillin in vitro. After Csk induction, the cells became spherical and more loosely attached to the culture substratum, and the alpha v beta 5 integrin complex (vitronectin receptor) of focal adhesions was redistributed to a novel type of structure consisting of punctate plaques on the ventral cell surface. These phenotypic changes occurred in several clones analyzed and were totally reversible when Csk was switched off, but they did not occur in cells overexpressing the catalytically inactive Csk R-222 mutant or luciferase. Our results thus show that a fraction of cellular Csk is targeted to focal adhesions via its SH2 and SH3 domains, probably interacting with tyrosyl-phosphorylated focal adhesion proteins. They also suggest that Csk is involved in the regulation of integrins controlling cell attachment and shape.

CSK Tyrosine-Protein Kinase↗