The hunting of the Src

  title={The hunting of the Src},
  author={G. Steven Martin},
  journal={Nature Reviews Molecular Cell Biology},
  • G. Martin
  • Published 2001
  • Biology
  • Nature Reviews Molecular Cell Biology
The non-receptor tyrosine kinase Src is important for many aspects of cell physiology. The viral src gene was the first retroviral oncogene to be identified, and its cellular counterpart was the first proto-oncogene to be discovered in the vertebrate genome. Src has been important, not only as an object of study in itself, but also as an entry point into the molecular genetics of cancer. 

Inhibition of proto-oncogene c-Src tyrosine kinase: toward a new antiarrhythmic strategy?

6 Regulation of Tyrosine Kinase Signaling by Cbl in Hematopoietic Stem Cells

Findings in v-Src highlight the critical importance of precise regulation of TK activities in order to avoid detrimental consequences to the homeostasis of the organisms.

Involvement of Src in the Adaptation of Cancer Cells under Microenvironmental Stresses

This paper focuses on the roles played by Src and other PTKs in cancer cell-specific behavior, that is, evasion of apoptosis or cell death under stressful extracellular and/or intracellular microenvironments (i.e., hypoxia, anoikis, hypoglycemia, and serum deprivation).

Retroviral oncogenes: a historical primer

Key features of all retroviral oncogenes were first identified in src, the oncogene of Rous sarcoma virus, including non-involvement in viral replication, coding for a single protein and cellular origin.

SRC in human carcinogenesis.

In a variety of tumor types including those derived from the colon and breast, the Src non-receptor tyrosine kinase is either overexpressed or constitutively active in a large percentage of the tumors.

Src in human carcinogenesis.

In a variety of tumor types including those derived from the colon and breast, the Src non-receptor tyrosine kinase is either overexpressed or constitutively active in a large percentage of the tumors.

Breakthroughs and Views Src protein – tyrosine kinase structure and regulation q

Protein–tyrosine phosphatases such as PTPa displace phosphotyrosine 527 from the Src SH2 domain and mediate its dephosphorylation leading to Src kinase activation.

Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites

Biophysical and biochemical studies show that caveolin-1 phosphorylation by Src at Tyr-14, followed by binding of the SH2 domain of activated Src to phospho–Tyr- 14, enhances Src–plasma membrane interaction, providing a mechanism that potentially regulates focal adhesion function.

Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation of the death accelerator Bik

It is shown that the observed Src-dependent resistance to cell death relies on Src ability to inhibit the mitochondrial pathway of apoptosis by specifically increasing the degradation rate of the BH3-only protein Bik, which could be a rate-limiting factor for apoptosis induction of tumor cells exhibiting deregulated Erk1/2 signaling.

Mechanisms of Oncogenesis by Retroviruses

Most replication-competent retroviruses cause cancer only after a long latent period, by insertional mutagenesis of the host genome, usually resulting in activation of a cellular proto-oncogene. In



Crystal structure of the Src family tyrosine kinase Hck

The crystal structure of the haematopoietic cell kinase Hck has been determined at 2.6/2.9 Å resolution and the conformation of the active site has similarities with that of inactive cyclin-dependent protein kinases.

Regulation, substrates and functions of src.

A novel viral oncogene with structural similarity to phospholipase C

The previously uncharacterized avian sarcoma virus CT10 is cloned and its genome is sequenced, revealing a protein, p47gag-crk, that has blocks of sequence similarity to the amino-terminal, non-catalytic region of the non-receptor class of tyrosine kinases.

Selected glimpses into the activation and function of Src kinase

The history behind the discovery and initial characterization of SRC and the regulatory mechanisms of Src activation, in particular, regulation by modification of the carboxy-terminal regulatory tyrosine by phosphatases and kinases are discussed.

Three-dimensional structure of the tyrosine kinase c-Src

The structure of a large fragment of the c-SRC tyrosine kinase, comprising the regulatory and kinase domains and the carboxy-terminal tail, has been determined and shows how appropriate cellular signals, or transforming mutations in v-Src, could break these interactions to produce an open, active kinase.

Requirement for c-ras proteins during viral oncogene transformation

The results show that transformation by three growth factor receptor-like oncogenes depends on c-ras proteins, while transformation by two cytoplasmic onCogenes appears to be independent ofc-ras protein.

Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein.

It is demonstrated that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.

Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates.

The development of a protein engineering-based method to identify the direct substrates of the prototypical protein tyrosine kinase v-Src, which controls fibroblast transformation by the Rous sarcoma virus, is described.