SRC is the symbol for the human gene homologous in sequence to the v-src gene of the Rous

sarcoma virus (also called avian sarcoma virus, ASV). The human protooncogene was assigned to

chromosome 20 by somatic cell hybrid studies. Le Beau et al. (1984) assigned SRC to 20q12-q13 by in

situ hybridization. Lebo et al. (1984) and Parker et al. (1985) confirmed the assignment by dual-beam

chromosome sorting and spot blot DNA analysis. LeBeau et al. (1985) found that deletions of 20q in

myeloid disorders were actually interstitial although they appeared to be terminal; thus, the interstitial

deletion had resulted in a shift at the SRC locus from 20q313 to the 20q breakpoint region. Azarnia et al.

(1988) foundthat overexpression of the SRC gene in NIH 3T3 cells caused reduction of cell-to-cell

transmission of molecules in the 400- to 700-dalton range. Down-regulation was enhanced by point

mutation of tyrosine-527, whereas mutation of tyrosine-416 suppressed both the down-regulation of

communication by the tyr-527 mutation and that by gene overexpression.The regulation of communication

by SRC may be important in the control of embryonic development and cellular growth. By in situ

hybridization, Morris et al. (1989) placed the SRC gene at 20q11.2. They observed a secondary peak of

grains in the region 20q13.2-qter, the localization of SRC suggested by previous in situ studies.

Furthermore, Morris et al. (1989)found that 1 allele of the SRC gene was lost in 2 patients with leukemia

and a deletion in 20q. They suggested that the deletions were interstitial. The new assignment, 20q11.2, is

consistentwith the assignment of HCK (142370) which presumably belongs to the same gene family,

having originated from a common ancestral gene.

By homologous recombination in mouse embryonic stem (ES) cells, Soriano et al. (1991)

produced mice carrying a null mutation in the SRC gene. Two independently targeted clones were

used to generate chimeras that transmitted the mutated allele to their offspring. Intercrossing

of heterozygotes gave rise to live-born homozygotes, but most of these mice died within the

first few weeks of birth. Histologic and hematologic examination of the homozygous mutants did

not show detectable abnormalities in the brain or platelets, where SRC is most highly expressed.

Deficiency in bone remodeling, indicating impaired osteoclast function and leading to

osteopetrosis, was found, however. These results showed that SRC is not required for general

cell viability, possibly because of functional overlap with other related tyrosine kinases such as

YES (164880), HCK, FGR, and LYN (165120), and uncovered an essential role for SRC in bone

formation. Lowe et al. (1993) used in vitro approaches and fetal liver transplantation into

irradiated SRC-deficient mice to demonstrate that the inherent defect resulting in osteopetrosis

is in osteoclasts and is autonomous of the bone marrow microenvironment. They identified a cell

type in which SRC function is essential and cannot be replaced by other related kinases. Lowe et

al. (1993) suggested that it should be possible to isolate the substrate that is specific to SRC.