Search PubMed⌕ Search

Biomedical subjects

F McKeon

Publications and source records attributed to F McKeon.

44 records · Page 3Linked to original sources
PubMed1991

Nuclear lamin proteins: domains required for nuclear targeting, assembly, and cell-cycle-regulated dynamics.

The nuclear lamin proteins assemble at the nuclear membrane into a highly dynamic network whose integrity is exquisitely controlled by the major cell cycle regulators. Although the actual cellular functions of the lamins remain elusive, the processes of targeted lamin assembly and phosphorylation-induced disassembly have come to light recently. These processes require functionally interacting lamin domains to execute targeting to the nucleus and the nuclear membranes, lamina assembly, and the disassembly response to cell-cycle-dependent phosphorylation.

Amino Acid Sequence↗
PubMed1990

Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.

The nuclear envelope is a dynamic structure that completely disassembles in response to MPF/cdc2 activity in mitosis. A key feature of this process is the hyperphosphorylation of the major structural proteins of the envelope, the nuclear lamins A, B, and C. Two highly conserved serine residues of the lamin protein (Ser-22 and Ser-392 of lamins A and C) are symmetrically positioned 5 amino acids from the ends of the large alpha-helical domain and are shown in the accompanying paper by Ward and Kirschner to be among four sites phosphorylated during nuclear envelope breakdown. Mutations in Ser-22 and Ser-392 that prevent phosphorylation at these sites block the disassembly of the nuclear lamina during mitosis. We propose a model for the regulation of lamin assembly in which phosphorylation just outside the ends of the alpha-helical domain controls the assembly dynamics of the lamin coiled-coil dimers.

Amino Acid Sequence↗
PubMed1989

The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope.

While the nuclear lamin proteins (A, B, and C) assemble specifically at the surface of the nuclear membrane, their sequences do not reveal stretches of hydrophobic amino acids that might explain their association with the nuclear membranes. However, the A and B lamin proteins possess Ras-like C-terminal CaaX sequence motifs, which in Ras proteins are sites of hydrophobic modifications required for membrane association and function. From the analysis of single and double lamin A mutants affecting the CaaX motif, the nuclear localization signal, and higher-order assembly properties, we propose that the CaaX motif functions as a nonspecific, low affinity membrane probe for proteins ultimately segregated to specific cellular membrane systems. Committed association with specific membranes requires additional interactions with membrane-resident factors.

Amino Acid Sequence↗
PubMed1988

Mutations in the nuclear lamin proteins resulting in their aberrant assembly in the cytoplasm.

We have constructed a series of mutations in the human A lamin cDNA to identify and alter the nuclear localization signal using an in vivo functional assay system. The nuclear localization signal in the lamin proteins has both structural and functional similarities with that of the SV40 large T-antigen. Mutations within this functional domain result in the assembly of cytoplasmic tubular structures, and the behavior of these mutants suggests a post-translational dimerization of the lamin proteins prior to their transport into the nucleus. In the course of this work other regions of the carboxy terminus of the A/C lamin proteins have been implicated in the proper assembly and structure of the nuclear envelope.

Amino Acid Sequence↗
PubMed1983

Anticentromere and anticentriole antibodies in the scleroderma spectrum.

We studied serum samples from 106 patients, including 80 in the scleroderma spectrum, by indirect immunofluorescent microscopy, using PtK1 rat kangaroo tissue culture cells as substrate. Anticentromere (Kinetochore) antibodies were present in 28 patients, and anticentriole antibodies were present in four patients. Anticentromere antibodies were usually present in patients with a benign, chronic form of systemic scleroderma, which has been termed the CREST (Calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia) syndrome. The four patients with a previously undescribed anticentriole antibody were all in the scleroderma spectrum. Possibly, these antibodies may have diagnostic and prognostic importance. Further, they will be useful in studying the structure and function of these cellular organelles.

Antibodies↗
PubMed1980

Immunological characteristics in cattle of allergens derived from smooth Brucella abortus S99.

Allergens prepared from a smooth strain of Brucella abortus (S99) were used in an intradermal test for the diagnosis of brucellosis in cattle. The development and testing of the allergen from the initial less purified stages is described. The removal of serological activity noted in some of the earlier preparations can be related to the elimination of molecules of high molecular weight. The final allergen is of a high order of sensitivity and specificity and does not cause production of complement fixing or agglutinating antibodies. Intradermal testing with such an allergen could be a most useful addition to present serological procedures as it could be carried out at the same time as tuberculin testing. As a routine surveillance test, particularly in low prevalence areas, it would eliminate the necessity for extensive blood sampling and in many cases detect the infected herd before serological tests would have become positive.

Agglutination Tests↗