Isolation and structural mapping of a human c-src gene homologous to the transforming gene (v-src) of Rous sarcoma virus

Gibbs, Carol P.; Tanaka, Akio; Anderson, Stephen; Radul, J.A.; Baar, Joseph; Ridgway, Anthony; Kung, Hsing-Jien; Fujita, Daishi

doi:10.1128/jvi.53.1.19-24.1985

Cited by 29 publications

(9 citation statements)

References 35 publications

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“…This was followed by the discovery that v-SRC is a tyrosine kinase protein, essential for cell transformation by the Rous sarcoma virus, and derived from cellular chicken c-SRC, incorporated into Rous sarcoma virus via recombination [2]. Human proto-oncogene tyrosine-protein kinase SRC (SRC), the first proto-oncogene, was described as highly structurally similar to chicken c-SRC [3,4]. As v-SRC contains an altered carboxy terminus compared to SRC, these amino acids were expected to play an important role in the regulation of SRC activity and cellular transformation [5].…”

Section: Introduction To Src and Src Family Kinasesmentioning

confidence: 99%

The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

Kock

Freson

2020

Medicina

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Proto-oncogene tyrosine-protein kinase SRC (SRC), as other members of the SRC family kinases (SFK), plays an important role in regulating signal transduction by different cell surface receptors after changes in the cellular environment. Here, we reviewed the role of SRC in platelets and megakaryocytes (MK). In platelets, inactive closed SRC is coupled to the β subunit of integrin αIIbβ3 while upon fibrinogen binding during platelet activation, αIIbβ3-mediated outside-in signaling is initiated by activation of SRC. Active open SRC now further stimulates many downstream effectors via tyrosine phosphorylation of enzymes, adaptors, and especially cytoskeletal components. Functional platelet studies using SRC knockout mice or broad spectrum SFK inhibitors pointed out that SRC mediates their spreading on fibrinogen. On the other hand, an activating pathological SRC missense variant E527K in humans that causes bleeding inhibits collagen-induced platelet activation while stimulating platelet spreading. The role of SRC in megakaryopoiesis is much less studied. SRC knockout mice have a normal platelet count though studies with SFK inhibitors point out that SRC could interfere with MK polyploidization and proplatelet formation but these inhibitors are not specific. Patients with the SRC E527K variant have thrombocytopenia due to hyperactive SRC that inhibits proplatelet formation after increased spreading of MK on fibrinogen and enhanced formation of podosomes. Studies in humans have contributed significantly to our understanding of SRC signaling in platelets and MK.

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Section: Introduction To Src and Src Family Kinasesmentioning

confidence: 99%

The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

Kock

Freson

2020

Medicina

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“…Since the 1970s, cancer research has advanced along with research about oncogenic RNA viruses such as Rous sarcoma virus, resulting in the identification of various cellular oncogenes. Researchers have identified the cellular oncogene c‐src on the Rous sarcoma virus‐encoded oncogene v‐src , which transforms cells and promotes the replication of proviruses integrated into the host genome 13,14 . RNA virus and cancer, thus, share a survival strategy of utilizing polynucleotide synthesis that is dependent on the RNA template.…”

Section: Introductionmentioning

confidence: 99%

RNA‐dependent RNA polymerase, RdRP, a promising therapeutic target for cancer and potentially COVID‐19

Machitani¹,

Yasukawa²,

Nakashima³

et al. 2020

Cancer Science

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A recent outbreak of coronavirus disease (COVID‐19) caused by the novel severe acute respiratory syndrome coronavirus 2 has driven a global pandemic with catastrophic consequences. The rapid development of promising therapeutic strategies against COVID‐19 is keenly anticipated. Family Coronaviridae comprises positive, single‐stranded RNA viruses that use RNA‐dependent RNA polymerase (RdRP) for viral replication and transcription. As the RdRP of viruses in this family and others plays a pivotal role in infection, it is a promising therapeutic target for developing antiviral agents against them. A critical genetic driver for many cancers is the catalytic subunit of telomerase: human telomerase reverse transcriptase (hTERT), identified initially as an RNA‐dependent DNA polymerase. However, even though hTERT is a DNA polymerase, it has phylogenetic and structural similarities to viral RdRPs. Researchers worldwide, including the authors of this review, are engaged in developing therapeutic strategies targeting hTERT. We have published a series of papers reporting that hTERT has RdRP activity and that this RdRP activity in hTERT is essential for tumor formation. Here, we review the enzymatic function of RdRP in virus proliferation and tumor development, reminding us of how the study of the novel coronavirus has brought us to the unexpected intersection of cancer research and RNA virus research.

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“…The c-src oncogene in humans has been molecularly cloned in its genomic form (20,41). The coding region consists of 11 exons (20), as was seen also in the chicken c-src gene (58).…”

mentioning

confidence: 97%

“…The c-src oncogene in humans has been molecularly cloned in its genomic form (20,41). The coding region consists of 11 exons (20), as was seen also in the chicken c-src gene (58). The human c-src coding region spans a distance of 19.5 kilobases (kb), more than three times that of the chicken c-src coding region (6 kb) (20,58).…”

mentioning

confidence: 99%

Expression of a Molecularly Cloned Human c-src Oncogene by Using a Replication-Competent Retroviral Vector

Tanaka

Fujita

1986

Molecular and Cellular Biology

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We studied the expression of a molecularly cloned human c-src gene, c-src-1, localized on chromosome 20, whose coding region consists of 11 exons and spans a 19.5-kilobase (kb) distance. Using a replication-competent retroviral vector derived from molecularly cloned Rous sarcoma virus DNA (pSRA-2), we obtained two constructs: one (pSR-CS) carrying the unmodified human c-src coding sequence and another (pSR-CVS) with a chimeric gene formed between the human c-src gene and the carboxy-terminal 12-amino acid v-src-specific coding sequence. From chicken embryo fibroblasts transfected with these DNA constructs, infectious viruses designated as WO CS and WO CVS, respectively, were recovered. WO CS virus did not cause cell transformation, whereas WO CVS induced cell transformation. Analyses of the proviral DNAs indicated that all introns were spliced out such that the 19-kb inserts were converted to 1.7-kb cDNA forms. Analyses of src proteins in infected cells, using monoclonal antibody MAb327 against v-src protein, showed the following results. The CVS and CS src proteins were about 60 and 61 kilodaltons in size, respectively; the specific protein kinase activity assayed in vitro of the CVS src protein was about 20-fold higher than that of the CS src protein and comparable to that of the v-src protein; the transforming CVS src protein reacted to an antibody against a v-src-specific peptide, whereas the CS src protein did not. These results indicate that the human c-src gene has a potential transforming ability and suggest that the v-src-specific sequence played an important role in the generation of Rous sarcoma virus.

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Isolation and structural mapping of a human c-src gene homologous to the transforming gene (v-src) of Rous sarcoma virus

Cited by 29 publications

References 35 publications

The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

RNA‐dependent RNA polymerase, RdRP, a promising therapeutic target for cancer and potentially COVID‐19

Expression of a Molecularly Cloned Human c-src Oncogene by Using a Replication-Competent Retroviral Vector

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