Transforming growth factor-β-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs.

The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ.

The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5.

ERK (extracellular-signal-regulated kinase) 4 [MAPK (mitogen-activated protein kinase) 4] and ERK3 (MAPK6) are atypical MAPKs. One major difference between these proteins and the classical MAPKs is substitution of the conserved T-X-Y motif within the activation loop by a single phospho-acceptor site within an S-E-G motif. In the present study we report that Ser(186) of the S-E-G motif in ERK4 is phosphorylated in vivo.

p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.

Protein degradation by basal constitutive autophagy is important to avoid accumulation of polyubiquitinated protein aggregates and development of neurodegenerative diseases. The polyubiquitin-binding protein p62/SQSTM1 is degraded by autophagy. It is found in cellular inclusion bodies together with polyubiquitinated proteins and in cytosolic protein aggregates that accumulate in various chronic, toxic, and degenerative diseases.

p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death.

Autophagic degradation of ubiquitinated protein aggregates is important for cell survival, but it is not known how the autophagic machinery recognizes such aggregates. In this study, we report that polymerization of the polyubiquitin-binding protein p62/SQSTM1 yields protein bodies that either reside free in the cytosol and nucleus or occur within autophagosomes and lysosomal structures. Inhibition of autophagy led to an increase in the size and number of p62 bodies and p62 protein levels.

Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.

The Phox and Bem1p (PB1) domain constitutes a recently recognized protein-protein interaction domain found in the atypical protein kinase C (aPKC) isoenzymes, lambda/iota- and zeta PKC; members of mitogen-activated protein kinase (MAPK) modules like MEK5, MEKK2, and MEKK3; and in several scaffold proteins involved in cellular signaling. Among the last group, p62 and Par6 (partitioning-defective 6) are involved in coupling the aPKCs to signaling pathways involved in cell survival, growth control, and cell polarity. By mutation analyses and molecular modeling, we have identified critical residues at the interaction surfaces of the PB1 domains of aPKCs and p62.

Purification and characterization of pancreatic elastase from North Atlantic salmon (Salmo salar).

An elastase I-like enzyme was purified to homogeneity from the pyloric caeca of North Atlantic salmon (Salmo salar) and compared with porcine elastase I. The molecular weight and isoelectric point were estimated to be 27 kDa and over 9.3, respectively.

Temperature and pH sensitivity of trypsins from Atlantic salmon (Salmo salar) in comparison with bovine and porcine trypsin.

Four differently charged trypsins were purified from pyloric caeca of Atlantic salmon (Salmo salar). The isoelectric points of three anionic isoforms were 4.70, 4.

Prognostic determinants in conventionally treated myocarditis and perimyocarditis--focus on antimyolemmal antibodies.

In this study from two specialized centres 85 patients with histologically proven myocarditis (n = 10) and clinically ascertained perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality; n = 75) were followed up for 4.5 + 1.9 years.

Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouse.

The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v.

Specific growth factor activity identifies and predicts murine mammary tumor.

In milk from substrains of mice with varying incidences of developing mammary tumor, we have isolated a specific mitogenic activity, which is unique in that it identifies mice with mammary tumor and predicts those mice that will eventually develop mammary tumor. None of the milk samples from control mice, who never developed mammary tumor, contained this specific predictive mitogenic activity. Chemical characterization has shown this specific mitogenic activity to be acid- and heat-stable and resistant to reducing agents.

The SCID-hu mouse: a small animal model for HIV infection and pathogenesis.

The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo. Multiple organs of the human hematolymphoid system have been successfully engrafted into the immunodeficient C.B-17 scid scid mouse, including fetal liver, thymus, lymph node, and skin.

Attenuation of exogenous murine mammary tumor virus virulence in the C3H/HeJ mouse substrain bearing the Lps mutation.

A major change in mammary tumor incidence (MTI) and latency has occurred in the C3H/HeJ mouse substrain maintained at The Jackson Laboratory. The average time required for 50% of the C3H/HeJ mice to develop a mammary tumor changed from 40 weeks of age to the current 61 weeks of age. This 61-week median MTI in the C3H/HeJ substrain is significantly different from the less than 40-week median MTI seen in other C3H substrains infected with an exogenous milk-transmitted murine mammary tumor virus (MuMTV).

The etiology of renal-cell carcinoma.

Experimental renal-cell carcinoma can be induced by many different chemical carcinogens; dimethyl nitrosoamine has been most studied. The disease so induced in experimental animals closely resembles the spontaneous disease in man in histopathology, course, and other characteristics. Two agents that are probably etiological of renal-cell cancer in man are tobacco and the analgesic, phenacetin; however, these materials can account for only a minority of the cases.

Transplantation of pancreatic islets into cleared mammary fat pads.

Hyperplastic islets of Langerhans from 129/J db3J/db3J mice were used to test the efficacy of the cleared mammary fat pad as an ectopic transplantation site. Eight to 10 islets were inoculated into a cleared mammary fat pad of syngeneic 129/J or allogeneic BALB/cByJ female mice following diabetes induction using streptozotocin. Islets transplanted into syngeneic hosts reversed the weight loss and hyperglycemia characteristic of nontransplanted streptozotocin-diabetic mice.

Development of carcinogen-induced skin tumors in mice with varied states of immune capacity.

The incidence of tumor formation in MCA-treated skin grafted onto maximally immunosuppressed mice that had been restored to varying extents with normal spleen cells was significantly greater in the mice with intermediate immune capacities than in those that had either minimal or maximal capacities. A similar biphasic tumor incidence curve was observed when MCA-treated skin was grafted onto mice of varying immune capacities, produced by thymectomy and varying doses of whole-body irradiation. Significantly more tumors occurred in the mice given moderate doses of irradiation than in tohse given higher or lower doses.

Primary tumor immunity in nude mice.

Tumor implants grew better in radiated or in newborn nu/nu mice than in adult nu/nu controls when, and only when, the tumors were demonstrably immunogenic in normal mice. This result suggests primary immunity. No evidence of immunological memory was found by immunization-challenge type experiments in the nude mice.

Differentiation of a methylcholanthrene-induced sarcoma to a benign plexiform fibroneural tumor in an adult frog (Rana pipiens). Possible influence of host regenerative capacity.

A spindle cell sarcoma appeared 20 months after implantation of a pellet of 3-methylcholanthrene in the denervated foreleg of an adult frog, Rana pipiens. Its growth rate and cellular structure were observed over the subsequent 19 months, the former remaining constant for the first 14 months, then slackening markedly during the final 4 months. Serial biopsies disclosed maturation to a well-differentiated fibroneural tumor of benign appearance, the change taking place notably during the period of decelerated growth rate.

Invasion and metastasis of a xenogeneic tumor in nude mice.

When aliquots of a malignant hamster tumor were transplanted to nude mice and to hamsters, the tumor showed 1) more rapid growth in the hamster, 2) local invasion and metastasis in both species, and 3) occasional spontaneous regression in the nude mouse.

Influence of regenerative capacity and innervation on oncogenesis in the adult frog (Rana pipiens).

Twenty-two sarcomas were induced in 19 adult frogs (Rana pipiens) treated with 3-methylcholanthrene pellets. Thirteen of these tumors arose first in a denervated forelimb, and only 2 arose first in normal or nerve-supplemented control forelimbs (P = 0.004).

Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse.

Dysplastic and malignant human breast tissues were grown successfully in the cleared mammary fat pads (CFP) of nude mice. The mammary fat pads were cleared while the mice were in a germfree isolator. Prepared mice were removed fron the germfree enviornment to facilitate transplantation of the human mammary tissue into their CFP and subsequently were maintained in sterile laminar flow racks.

Husbandry of the "nude" mouse in conventional and germfree environments.

The "nude" mouse is a unique tool for immunologic studies. Its relatively short life span dictates the application of rigid environmental controls to increase longevity if the mouse is to assume the role of a practical experimental animal. In this paper we discussed the husbandry procedures employed to raise "nude" mice in our facilities under conventional, defined flora, and germfree conditions.