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 in, role, immune and/or system:
“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)
“Friends serve central functions for children that parents do not, and they play a critical role in shaping children’s social skills and their sense of identity. . . . The difference between a child with close friendships and a child who wants to make friends but is unable to can be the difference between a child who is happy and a child who is distressed in one large area of life.”
—Zick Rubin (20th century)
“Certainly parents play a crucial role in the lives of individuals who are intellectually gifted or creatively talented. But this role is not one of active instruction, of teaching children skills,... rather, it is support and encouragement parents give children and the intellectual climate that they create in the home which seem to be the critical factors.”
—David Elkind (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)
“He could jazz up the map-reading class by having a full-size color photograph of Betty Grable in a bathing suit, with a co- ordinate grid system laid over it. The instructor could point to different parts of her and say, “Give me the co-ordinates.”... The Major could see every unit in the Army using his idea.... Hot dog!”
—Norman Mailer (b. 1923)