Disease relevance of Src64B

• The acutely-transforming avian virus, Rous sarcoma virus, arose as the result of the transduction of the c-src gene of the chicken by a relatively benign avian leucosis virus [1].
• Involvement of FAK/Src complex in the processes of Escherichia coli phagocytosis by insect hemocytes [2].

High impact information on Src64B

• Drosophila ring canal growth requires Src and Tec kinases [3].
• We conclude that c-src may not be a mitotic signal but instead may play a role in the development of neural tissue and smooth muscle [4].
• Drosophila c-src RNA is abundant in embryos and pupae but rare in larvae and adults [4].
• The nucleotide sequence and the tissue-specific expression of Drosophila c-src [4].
• We have examined the coding capability and expression of the Drosophila homolog of the vertebrate proto-oncogene c-src [4].

Biological context of Src64B

• In Drosophila, Src64 controls complex morphological events that occur during oogenesis [5].
• These results uncover novel roles for both Csk and Src64 in a dynamic event that involves adhesion, communication between cell types and control of cell motility [5].
• Drosophila Src-family kinases function with Csk to regulate cell proliferation and apoptosis [6].
• The Tec29 tyrosine kinase is required during Drosophila embryogenesis and interacts with Src64 in ring canal development [7].
• Two cloned Drosophila sequences, Dash and Dsrc, were previously isolated by hybridization to the viral oncogenes v-abl and v-src [8].

Anatomical context of Src64B

• Csk differentially regulates Src64 during distinct morphological events in Drosophila germ cells [5].
• These data, along with changes in G-actin accumulation in the oocyte nucleus, suggest that Src64 is involved in a nuclear actin function during karyosome condensation [9].
• Src family tyrosine kinases respond to a variety of signals by regulating the organization of the actin cytoskeleton [9].
• The results are discussed in relation to potential roles for the vertebrate homologues of Drk and Csw (Grb2 and SHP2, respectively) in the transformation of fibroblasts by vertebrate Src [10].
• Analogous mutations in Drosophila Src64 (DSrc) induce abnormal differentiation of photoreceptor cells when expressed ectopically in the developing Drosophila adult eye [10].

Associations of Src64B with chemical compounds

• The Src family protein tyrosine kinases (SFKs) are crucial regulators of cellular morphology [5].
• This novel APPL-interacting protein 1 (APLIP1) contains a Src homology 3 domain and a phosphotyrosine interaction domain and is expressed abundantly in neural tissues [11].

Enzymatic interactions of Src64B

• Src64 regulates this process by phosphorylating Y677 within the kinase domain of Tec29, an event required for Tec29 activation [12].

Regulatory relationships of Src64B

• Recent studies have identified key Src64-dependent mechanisms that regulate actin cytoskeletal dynamics during the growth of actin-rich ring canals, which act as intercellular bridges between germ cells [5].
• We find that dominant-negative mutations in either the drk or csw genes ameliorate the developmental abnormalities induced by activated DSrc [10].

Other interactions of Src64B

• Overexpression of either wild-type Drosophila SFK (Src64 and Src42) is sufficient to induce ectopic proliferation in G1/G0-arrested, uncommitted cells in eye imaginal discs [6].
• Strikingly, Src64 and Csk function in the germline to control packaging, not in migrating follicle cells, suggesting novel functions for this signaling cassette in regulating dynamic adhesion [5].
• Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases [10].
• Upon stimulation of the bombesin receptors, KUZ increases the docking and activation of adaptors Src homology 2 domain-containing protein and Gab1 on the EGFR, and activation of Ras and Erk [13].
• Alignment of the predicted amino acid sequences in the homologous regions shows amino acid sequence identities of 74% between Dash and the 5' portion of v-abl and of 54% between Dsrc and 3' portion of v-src [8].

Analytical, diagnostic and therapeutic context of Src64B

• The consequences of deregulated Src activity have been studied extensively in cell culture; however, the effects of this deregulation in vivo, as well as the mechanisms of Src-induced tumorigenesis, remain poorly understood [6].
• In situ hybridization reveals that after the first 8 hr of development, c-src RNA accumulates almost exclusively in neural tissues such as the brain, ventral nerve chord, and eye-antennal discs, and in differentiating smooth muscle [4].
• Sequence analysis of a cDNA clone representing the Drosophila c-src locus suggests that the gene encodes a 62 kd protein that is remarkably similar to the protein product of chicken c-src [4].

References