This was of significant interest because ITGA9 has only been reported to dimerize with ITGB1, and as noted, RPMI 8866 cells have low to undetectable levels of ITGB1, in agreement with the fact that anti-ITGB1 antibodies have no effect on RPMI 8866 adhesion to multiple substrates, including ADAMs [36], [39].
For example, tumor necrosis factor-α converting enzyme (TACE/ADAM17) is essential for the phorbol ester stimulated shedding of the ectodomains of various membrane-anchored proteins [10], and Kuzbanian/ADAM10 is involved in the ectodomain shedding of multiple substrates, including ephrin, Notch ligands, and cadherins [11] [15].
Together, these phosphorylation signals enable parkin to ubiquitinate multiple substrates, including several involved in mitochondrial homoeostasis.
PAKs are serine/threonine kinases that phosphorylate multiple substrates, including those that are involved in cytoskeletal reorganization, cell proliferation, and survival.
Mammalian cells are generally cultured in complex media containing multiple substrates, including glucose, glutamine (and other amino acids), fatty acids and organic acids.
As an E3 ligase anchored onto the mitochondrial outer membrane, MUL1 has been shown to have multiple substrates including Drp1 and Mfn (Braschi et al., 2009; Lokireddy et al., 2012).
Activated Lck, Fyn, and ZAP-70 then phosphorylate multiple downstream substrates, including linker for activation of T cells (LAT) and the tyrosine kinase Pyk2 [7], [8], [8].
As a result, both known and unique substrates, including multiple centrosomal substrates for Syk were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity [ 28].
GSK-3β has been implicated in multiple biological processes because it phosphorylates a broad range of substrates including several differentiation checkpoints including c-Myc, snail and PI3K [ 23].
However, several putative SRC substrates, including HIPK3, STAT5A, p120, FRK and Hrs, were frequently phosphorylated in multiple breast tumors.
14, 15, 27 FADS2, which is expressed in multiple tissues including liver, brain and skin, is known to catalyze desaturation of at least five distinct substrates including linoleate, linolenate and palmitate.
