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Receptor desensitization is accomplished by accelerated endocytosis and degradation of ligand-receptor complexes. An in vitro reconstituted system indicates that Cbl adaptor proteins directly control downregulation of the receptor for the epidermal growth factor (EGFR) by recruiting ubiquitin-activating and -conjugating enzymes. We infer a sequential(More)
Subgroup C strains of Herpesvirus saimiri, a leukemogenic virus of non-human primates, transform human T cells to permanent growth in culture. These cell retain their antigen specificity, and they are becoming widely used as a model for activated human T cells. Though a variety of human cell types can be infected by H. saimiri, transformation appears to be(More)
The proto-oncogenic protein c-Cbl was discovered as the cellular form of v-Cbl, a retroviral transforming protein. This was followed over the years by important discoveries, which identified c-Cbl and other Cbl-family proteins as key players in several signaling pathways. c-Cbl has donned the role of a multivalent adaptor protein, capable of interacting(More)
Following discovery of c-Cbl, a cellular form of the transforming retroviral protein v-Cbl, multiple Cbl-related proteins have been identified in vertebrate and invertebrate organisms. c-Cbl and its homologues are capable of interacting with numerous proteins involved in cell signaling, including various molecular adapters and protein tyrosine kinases. It(More)
The Src family of tyrosine protein kinases (TPKs) represents a class of closely related intracellular enzymes that participate in the signal transduction pathways in a variety of hemopoietic cells. The Src TPKs associate with multiple cell surface molecules rendering these receptors capable of activating tyrosine phosphorylation of cellular protein targets.(More)
Protooncogenic protein c-Cbl undergoes tyrosine phosphorylation in response to stimulation through the receptors for antigens, immunoglobulins, cytokines, and growth factors as well as through the integrins. Tyrosine phosphorylation of c-Cbl may play a functional role in signal transduction, since c-Cbl interacts with many crucial signaling molecules(More)
Investigation of human activated T cells has been complicated by the need for periodic restimulation with Ag/mitogen and accessory cells and by the limited life span of most human T cell clones. To overcome these problems, we have transformed established human T cell clones to permanent growth with Herpesvirus saimiri, a lymphoma-inducing virus of nonhuman(More)
Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models,(More)
HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in(More)
The Cbl protein is a key player in macrophage colony-stimulating factor (M-CSF)-induced signaling. To examine the role of Cbl in M-CSF-mediated cellular events, we used Cbl(YF/YF) knockin mice in which the regulatory tyrosine 737, which when phosphorylated binds to the p85 subunit of phosphatidylinositol 3 kinase (PI3K), is substituted to phenylalanine. In(More)