+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Shc and FAK differentially regulate cell motility and directionality modulated by PTEN

, : Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. The Journal of Cell Biology 146(2): 9-403

Cell migration is modulated by regulatory molecules such as growth factors, oncogenes, and the tumor suppressor PTEN. We previously described inhibition of cell migration by PTEN and restoration of motility by focal adhesion kinase (FAK) and p130 Crk-associated substrate (p130(Cas)). We now report a novel pathway regulating random cell motility involving Shc and mitogen-activated protein (MAP) kinase, which is downmodulated by PTEN and additive to a FAK pathway regulating directional migration. Overexpression of Shc or constitutively activated MEK1 in PTEN- reconstituted U87-MG cells stimulated integrin- mediated MAP kinase activation and cell migration. Conversely, overexpression of dominant negative Shc inhibited cell migration; Akt appeared uninvolved. PTEN directly dephosphorylated Shc. The migration induced by FAK or p130(Cas) was directionally persistent and involved extensive organization of actin microfilaments and focal adhesions. In contrast, Shc or MEK1 induced a random type of motility associated with less actin cytoskeletal and focal adhesion organization. These results identify two distinct, additive pathways regulating cell migration that are downregulated by tumor suppressor PTEN: one involves Shc, a MAP kinase pathway, and random migration, whereas the other involves FAK, p130(Cas), more extensive actin cytoskeletal organization, focal contacts, and directionally persistent cell motility. Integration of these pathways provides an intracellular mechanism for regulating the speed and the directionality of cell migration.


PMID: 10427092

DOI: 10.2307/1619315

Other references

Alonso M.T.rres; Martnez Alvarez J.A., 1969: Structural data on the lower valley of the Nalon and Narcea rivers, Asturias. Hercynian folds and thrusts, Cantabrian fault, stratigraphic summary, Precambrian-Tertiary, Spain.

Vasilescu, N.; Draghia, L., 1995: Research concerning land property in Vrancea district. The paper describes the settlement and population distribution, and the agricultural production structure of the various ecological zones of Vrancea district, Romania. The number, size and characteristics of the different forms of agricultural ent...

Schubert, G.E., 1956: Sliding hernia and simulated sliding hernia. Deutsches Medizinisches Journal 7(7): 179-182

Caldwell, J.S.; Lutz, J.M.; Moon, H.H.; Culpepper, C.W., 1940: Comparative studies of varietal suitability for freezing preservation of peas, green or snap beans, lima beans, and sweet corn grown under eastern conditions. 18 vars. of peas, 14 of green beans, 8 of lima beans, and 35 of sweet corn were used in work continued over 2 seasons. Material was examined after 6 to 7 months' storage at 0[degree]F. Each of the crops, except corn, showed wide range in appe...

Dell, D.L.; Chen, H.; Ahmad, F.; Stewart, D.E., 2000: Knowledge about human papillomavirus among adolescents. Objective: To assess knowledge of human papillomavirus (HPV) among high school-aged adolescents. Methods: We administered written surveys to 523 inner-city high school students in Toronto, Canada, that asked about HPV, other sexually transmitted d...

Rodríguez Villamizar, L.Andrea.; Ruiz-Rodríguez, M.; Jaime García, Mía.Leonor., 2011: Benefits of combining methods to analyze the causes of maternal mortality, Bucaramanga, Colombia. Define critical points of change in the maternal care process, guide decision-making in this area, and support the strengthening of service delivery policies, with a view to achieving the Millennium Development Goal of improving maternal health. R...

Nam, E.Jeong.; Han, S.Woo.; Kim, S.Uk.; Cho, J.Hee.; Sa, K.Hee.; Lee, W.Kee.; Park, J.Yong.; Kang, Y.Mo., 2006: Association of vascular endothelial growth factor gene polymorphisms with behcet disease in a Korean population. Vascular endothelial growth factor (VEGF) is important for angiogenesis and inflammation, both of which are codependent and contribute to the pathophysiology of Behcet disease (BD). The increased expressions of VEGF have been observed in the activ...

Zhou, Z.; Zou, Y.; Liu, G.; Zhou, J.; Wu, J.; Zhao, S.; Su, Z.; Gu, X., 2017: Mutation-profile-based methods for understanding selection forces in cancer somatic mutations: a comparative analysis. Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rat...

Williams, S.M.; Parry, B.R.; Schlup, M.M., 1992: Quality control: an application of the cusum. Bmj 304(6838): 1359-1361

Colliot, P.; Chokron, S.; Ohlmann, Téophile., 2002: Is there an effect of handedness on the position of the egocentric reference?. Forty normal subjects (20 left-handed; 20 right-handed) were submitted to a proprioceptive straight ahead pointing task while blindfolded to study the effect of the hand used and of the hand preference on the estimation of the subjective sagittal...