Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by association with a variety of tyrosine kinase receptors and intracellular tyrosine-phosphorylated substrates. We isolated a cDNA that encodes a 50-kDa regulatory subunit of PI 3-kinase with an expression cloning method using 32 P-labeled insulin receptor substrate-1 (IRS-1). This 50-kDa protein contains two SH2 domains and an inter-SH2 domain of p85␣, but the SH3 and bcr homology domains of p85␣ were replaced by a unique 6-amino acid sequence. Thus, this protein appears to be generated by alternative splicing of the p85␣ gene product. We suggest that this protein be called p50␣. Northern blotting using a specific DNA probe corresponding to p50␣ revealed 6.0-and 2.8-kb bands in hepatic, brain, and renal tissues. The expression of p50␣ protein and its associated PI 3-kinase were detected in lysates prepared from the liver, brain, and muscle using a specific antibody against p50␣. Taken together, these observations indicate that the p85␣ gene actually generates three protein products of 85, 55, and 50 kDa. The distributions of the three proteins (p85␣, p55␣, and p50␣), in various rat tissues and also in various brain compartments, were found to be different. Interestingly, p50␣ forms a heterodimer with p110 that can as well as cannot be labeled with wortmannin, whereas p85␣ and p55␣ associate only with p110 that can be wortmanninlabeled. Furthermore, p50␣ exhibits a markedly higher capacity for activation of associated PI 3-kinase via insulin stimulation and has a higher affinity for tyrosinephosphorylated IRS-1 than the other isoforms. Considering the high level of p50␣ expression in the liver and its marked responsiveness to insulin, p50␣ appears to play an important role in the activation of hepatic PI 3-kinase. Each of the three ␣ isoforms has a different function and may have specific roles in various tissues.A variety of growth factors and hormones mediate their cellular effects via interactions with cell surface receptors that possess protein kinase activity (1, 2). The interaction of most of these ligands with their receptors induces tyrosine kinase activation and autophosphorylation of the receptor, resulting in physical association of these receptors with several cytoplasmic substrates having SH2 domains. Phosphatidylinositol 3-kinase (PI 3-kinase) 1 has been identified through its ability to associate with cellular protein kinases, including numerous growth factor receptors and oncogene products (3, 4). This lipid kinase phosphorylates phosphatidylinositol at the D-3 position of the inositol ring in response to stimulation with a variety of growth factors and hormones (5). Although the role of this lipid product in cellular regulation remains unclear, recent reports suggest that the activation of PI 3-kinase leads to the activation of c-Akt, Rac, PKC-␥ isoform, and p70 S6 kinase (6 -9). As a result, PI 3-kinase has been suggested to play essential roles in the regulation of various cellular activities, including proliferation (10, 11), differen...

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Propri\'et\'es topologiques des polyn\^omes de deux variables complexes, et automorphismes alg\'ebriques de l'espace $C^{2}$ By Masakazu SUZUKI ( Re\cau le 5 sept. , 1972) Introduction.Les recherches r\'ecentes, dues \'a T. Nishino et H. Sait\^o1), sur les fonctions enti\'eres de deux variables complexes, indiquent que les singularit\'es2) de ces fonctions sont soumises \'a certaines restrictions, caus\'ees par la topologie de l'espase $C^{2}$ . A. Gutwirth, M. Nagata et I. Wakabayashi ont aussi rencontr\'e un probl\'eme de ce caract\'ere3).Or, pour les (bonnes) fonctions r\'eelles, c'\'etait l'id\'ee fondamentale, due \'a M. Morse4), de d\'eterminer le type topologique de l'espace o\'u est d\'efinie la fonction consid\'er\'ee (et celui des sous-vari\'et\'es niveaux), d'apr\'es les types de singularit\'es de la fonction.Dans le Pr\'esent m\'emoire, en appliquant cette id\'ee aux fonctions poly-n\^omes de deux variables complexes, nous trouverons deux esp\'eces de restrictions auxquelles sont soumises les singularit\'es de ces fonctions; l'une est l'ind\'ependance, \'a un certain sens, des l-cycles homologiques engendr\'es aux points singuliers de la fonction consid\'er\'ee (voir les \S \S 2, 3), et l'autre concerne l'existence de la singularit\'e au point \'a l'infini (le \S 4). Nos r\'esultats donnent aussi une solution au probl\'eme cit\'e plus haut, qui est reli\'e aux automorphismes alg\

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Blended films of poly(L-lactide) [ie poly(L-lactic acid)] (PLLA) and poly(ε ε ε ε ε ε-caprolactone) (PCL) without or mixed with 10 wt% poly(L-lactide-co-ε ε ε ε ε ε-caprolactone) (PLLA-CL) were prepared by solution-casting. The effects of PLLA-CL on the morphology, phase structure, crystallization, and mechanical properties of films have been investigated using polarization optical microscopy, scanning electron microscopy, differential scanning calorimetry and tensile testing. Addition of PLLA-CL decreased number densities of spherulites in PLLA and PCL films, and improved the observability of spherulites and the smoothness of cross-section of the PLLA/PCL blend film. The melting temperatures (T m ) of PLLA and PCL in the films remained unchanged upon addition of PLLA-CL, while the crystallinities of PLLA and PCL increased at PLLA contents [X PLLA = weight of PLLA/(weight of PLLA and PCL)] of 0.4-0.7 and at most of the X PLLA values, respectively. The addition of PLLA-CL improved the tensile strength and the Young modulus of the films at X PLLA of 0.5-0.8 and of 0-0.1 and 0.5-0.8, respectively, and the elongation at break of the films at all the X PLLA values. These findings strongly suggest that PLLA-CL was miscible with PLLA and PCL, and that the dissolved PLLA-CL in PLLA-rich and PCL-rich phases increased the compatibility between these two phases.