The human SRC gene encodes a non-receptor protein tyrosine kinase that participates in multiple signaling pathways involved in gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, cell migration, and transformation. SRC is overexpressed or activated in multiple human malignancies, including a high incidence in colorectal cancers. The highest-scoring orthologous gene in Drosophila is Src64B, for which multiple genetic reagents have been generated, including loss-of-function alleles, RNAi-targeting and over-expression constructs, and alleles caused by insertional mutagenesis. The Drosophila Src42A gene has also been used in a SRC-related disease model; while ortholgous to human SRC, Dmel\Src42A is more closely related to the human Src family genes FRK and FYN. There are multiple other paralogous and orthologous genes in both species.
The human SRC gene has not been introduced into flies.
Animals homozygous for an amorphic allele of Dmel\Src64B survive to adulthood; female fertility is severely reduced. Using eye and wing discs, clones of cells overexpressing Src64B have been generated; consistent with previous findings, these clones are virtually eliminated from the tissue during development. However, wild-type cells surrounding Src64B-expressing clones significantly overgrow; in the eye, this results in an aberrant 'folded-eye' phenotype; similar results are obtained in the wing disc. Thus, elevated SRC expression in clones of cells results in growth disadvantage cell-autonomously, but stimulates overgrowth of surrounding wild-type tissue non-cell-autonomously. The fly system has been used to characterize the roles of JNK signaling (using Dmel\bsk) and Hippo signaling (using Dmel\yki) pathways in this intercellular interaction process.
The role of SRC has also been investigated using expression of a constitutively active allele of Src42A in a portion of the wing disc. Src42A activates Drosophila MAP kinases rl and p38b in the wing disc, both cell autonomously and non-autonomously. This work identified a MAP3K9 Drosophila ortholog, slpr, as playing a downstream role in Src42A-induced overproliferation; knockdown of slpr suppresses Src42A-induced non-cell autonomous activation of p38b but not of rl nor of a JNK signaling marker (Dmel\bsk).
[updated Jun. 2021 by FlyBase; FBrf0222196]
The SRC gene is frequently implicated in cancer. [from MIM:190090; 2017.01.17]
The SRC protein participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. [from Gene Cards, SRC; 2017.01.17]
The SRC gene encodes a nonreceptor tyrosine kinase homologous in sequence to the v-src gene of the Rous sarcoma virus. [from MIM:190090; 2017.01.17]
Many to many: multiple paralogs and orthologs in both species.
Highest-scoring ortholog of human gene SRC (many to many; multiple paralogs and orthologs in both species). Dmel\Src64B shares 50% identity and 67% similarity with human SRC.
High-scoring ortholog of human FRK; moderate-scoring ortholog of FYN, YES1 and SRC (multiple related genes in both species). Dmel\Src42A shares 46-58% identity and 60-74% similarity with the human genes.
