Role in The Immune System and Apoptosis
Selectins, a group of proteins that are involved in leukocyte rolling towards a source of inflammation, contain an EGF-like domain along with a lectin domain and short consensus repeats (SCRs). The functions of the EGF-like domain vary between different selectin types. Kansas and co-workers were able to show that the EGF-like domain is not required for maximal cellular adhesion in L-selectin (expressed on lymphocytes). However, it is involved in both ligand recognition and adhesion in P-selectin (expressed on platelets) and may also be involved in protein-protein interactions. It has been suggested that the interactions between lectin domains and carbohydrate ligands might be calcium-dependent.
Interestingly, immature human dendritic cells appear to require interactions with the EGF-like domains of selectins during their maturation process. Blocking of this interaction with monoclonal anti-EGF-like domain antibodies prevents dendritic cell maturation. The immature cells fail to activate T-cells and produce less interleukin 12 than wild-type dendritic cells.
Phan et al. could show that the artificial insertion of an N-glycosylation site into the EGF-like domains in P- and L-selectins increased the affinities of selectins to their ligands and led to slower rolling. Therefore, EGF-like domains seem to play a crucial role in leukocyte movements towards inflammatory stimuli.
The EGF-like domain is also part of laminins, an important group of extracellular proteins. The EGF-like domains are usually masked in intact membranes, but become exposed when the membrane is destroyed, e.g. during inflammation, thereby stimulating membrane growth and restoring damaged membrane parts.
Moreover, the EGF-like domain repeats of the stabilin-2 domain have been shown to specifically recognize and bind apoptotic cells, probably by recognizing phosphatidylserine, an apoptotic cell marker (“eat me-signal”). Park et al. further demonstrated that the domains are able to competitively impair recognition of apoptotic cells by macrophages.
In conclusion, the EGF-like domain appears to play a vital role in immune responses as well as in eliminating dead cells in the organism.
Read more about this topic: EGF-like Domain
Famous quotes containing the words role in the, role, immune and/or system:
“Language makes it possible for a child to incorporate his parents’ verbal prohibitions, to make them part of himself....We don’t speak of a conscience yet in the child who is just acquiring language, but we can see very clearly how language plays an indispensable role in the formation of conscience. In fact, the moral achievement of man, the whole complex of factors that go into the organization of conscience is very largely based upon language.”
—Selma H. Fraiberg (20th century)
“Always and everywhere children take an active role in the construction and acquisition of learning and understanding. To learn is a satisfying experience, but also, as the psychologist Nelson Goodman tells us, to understand is to experience desire, drama, and conquest.”
—Carolyn Edwards (20th century)
“The moral immune system of this country has been weakened and attacked, and the AIDS virus is the perfect metaphor for it. The malignant neglect of the last twelve years has led to breakdown of our country’s immune system, environmentally, culturally, politically, spiritually and physically.”
—Barbra Streisand (b. 1942)
“Our system of government, in spite of Vietnam, Cambodia, CIA, Watergate, is still the best system of government on earth. And the greatest resource of all are the 215 million Americans who still have within us the strength, the character, the intelligence, the experience, the patriotism, the idealism, the compassion, the sense of brotherhood on which we can rely in the future to restore the greatness to our country.”
—Jimmy Carter (James Earl Carter, Jr.)