Open Close
General Information
Name
cancer, intercellular interactions, SRC-related
FlyBase ID
FBhh0001074
Disease Ontology Term
Parent Disease
OMIM
Overview

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]

Disease Summary Information
Disease Summary: cancer, intercellular interactions, SRC-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

The SRC gene is frequently implicated in cancer. [from OMIM:190090; 2017.01.17]

Genetics
Cellular phenotype and pathology
Molecular information

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 OMIM:190090; 2017.01.17]

External links
Disease synonyms
Search term: non-autonomous proliferation
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to many: multiple paralogs and orthologs in both species.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (2)
      Gene Snapshot
      Src oncogene at 64B (Src64B) encodes a Src family nonreceptor tyrosine kinase. It has many biological roles, including ring canal morphogenesis in oogenesis and the male germline, microfilament ring constriction during cellularization, and modulation of growth and apoptosis. Some of its roles overlap with those of the product of Src42A. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)

      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.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Src oncogene at 42A (Src42A) encodes the none-receptor tyrosine kinase regulating cell proliferation, cell adhesion and morphogenetic processes including dorsal closure, tracheal tube size control and germ band elongation. It is regulated by both inhibitory and activating tyrosine phosphorylation. [Date last reviewed: 2019-09-26]
      Gene Groups / Pathways
      Comments on ortholog(s)

      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.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (31 groups)
        protein-protein
        Interacting group
        Assay
        References
        enzymatic study, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot
        two hybrid, pull down, anti tag western blot
        pull down, anti tag western blot
        enzymatic study, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot, two hybrid
        anti tag coimmunoprecipitation, western blot, multidimensional protein identification technology
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        protein-protein
        Interacting group
        Assay
        References
        enzymatic study, western blot, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, western blot, pull down
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, anti tag western blot, two hybrid
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, pull down
        enzymatic study, autoradiography, western blot
        enzymatic study, autoradiography
        enzymatic study, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (10 alleles)
        Models Based on Experimental Evidence ( 4 )
        Modifiers Based on Experimental Evidence ( 5 )
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 4 )
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - genetic evidence
        ends-out gene targeting
        ethyl methanesulfonate
        loss of function allele
        References (9)