Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival and hemangiosarcoma formation

John C. Morgan, John E. Majors, Deni S. Galileo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The cellular proto-oncogene c-src is thought to be involved in formation, progression, and metastasis of a variety of tumor cell types, although its exact role during tumor cell genesis is not well defined. v-src, the viral oncogene counterpart of c-src, causes metastatic sarcomas, hemorrhagic disease, and hemangiosarcomas in chicken embryos and, thus, can be used as a constitutively activated form of src for experimentally-induced tumorigenesis. Here, we used retroviral vectors to express wild-type v-src or SH2 or SH3 domain-deleted forms (ΔSH2 or ΔSH3) to determine if different pathogenic effects resulted. Vectors were injected into early chick embryo midbrain ventricles and embryos were sacrificed at various ages up to embryonic day (E) 18. Retroviral expression of all forms of v-src resulted in transformation of pial connective tissue cells into large, rounded abnormal-appearing cells. Surprisingly, all forms of v-src were lethal. The v-src retrovirus was lethal and killed most embryos by E15 with the development of hemangiosarcomas over the injection site between E10-E12. The ΔSH3 retrovirus was the most deadly, killing most embryos by E12, however, it never resulted in hemangiosarcoma formation. The ΔSH2 retrovirus injected embryos survived longer than v-src or ΔSH3 embryos, and some of these embryos also developed large hemangiosarcomas over the injection site between E13 and E18. These results demonstrate that the src SH2 domain is required to be fully lethal, whereas the presence of the SH3 domain attenuated lethality. Furthermore, the formation of hemangiosarcomas absolutely required the presence of the src SH3 domain and to some extent required the SH2 domain. This implicates distinct and opposite roles for SH2 and SH3 domains of src and their cellular binding partners in tumorigenesis and hemorrhagic disease.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
JournalClinical and Experimental Metastasis
Issue number2
StatePublished - Jan 2005


  • Chicken embryo
  • Hemangiosarcoma
  • Retroviral vector
  • c-src
  • v-src

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival and hemangiosarcoma formation'. Together they form a unique fingerprint.

Cite this