A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin.

Abstract

We used complementary biochemical and immunological techniques to establish that an endothelial cell transmembrane glycoprotein, GP116, is a CD44-like molecule and binds directly both to extracellular matrix components (e.g., hyaluronic acid) and to ankyrin. The specific characteristics of GP116 are as follows: (i) GP116 can be surface labeled with Na125I and contains a wheat germ agglutinin-binding site(s), indicating that it has an extraceHlular domain; (ii) GP116 displays immunological cross-reactivity with a panel of CD44 antibodies, shares some peptide similarity with CD44, and has a similar 52-kDa precursor molecule, indicating that it is a CD44-like molecule; (iii) GP116 displays specific hyaluronic acid-binding properties, indicating that it is a hyaluronic acid receptor; (iv) GP116 can be phosphorylated by endogenous protein kinase C activated by 12-O-tetradecanoylphorbol-13-acetate and by exogenously added protein kinase C; and (v) GP116 and a 20-kDa tryptic polypeptide fragment of GP116 from the intracellular domain are capable of binding the membrane-cytoskeleton linker molecule, ankyrin. Furthermore, phosphorylation of GP116 by protein kinase C significantly enhances GP116 binding to ankyrin. Together, these findings strongly suggest that phosphorylation of the transmembrane glycoprotein GP116 (a CD44-like molecule) by protein kinase C is required for effective GP116-ankyrin interaction during endothelial cell adhesion events.

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

“…These molecules belong to a family of related genes that probably arose by duplication and divergence of a common ancestral gene. Ankyrin is known to bind to a number of plasma membrane–associated proteins including the following: band 3, two other members of the anion exchange gene family (Bennet, 1992), Na + /K + -ATPase (Nelson and Veshnock 1987; Zhang et al 1998), the amiloride-sensitive Na + channel (Smith et al 1991), the voltage-dependent Na + channel (Kordeli et al 1995), Ca 2+ channels (Bourguignon et al 1993b, Bourguignon et al 1995a; Bourguignon and Jin 1995) and the adhesion molecule CD44 (Bourguignon et al 1986, Bourguignon et al 1991, Bourguignon et al 1992, Bourguignon et al 1993a; Kalomiris and Bourguignon 1988, Kalomiris and Bourguignon 1989; Lokeshwar and Bourguignon 1991, Lokeshwar and Bourguignon 1992; Lokeshwar et al 1994, Lokeshwar et al 1996). It has been suggested that the binding of ankyrin to certain membrane-associated molecules is necessary for signal transduction, cell adhesion, membrane transport, cell growth, migration, and tumor metastasis (Bennet, 1992; Bourguignon et al 1995b, 1996, Bourguignon et al 1997, Bourguignon et al 1998a; De Matteis and Morrow 1998; Zhu and Bourguignon 1998, Zhu and Bourguignon 2000).…”

Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression

“…Coordinated RhoGTPase signaling is considered to be a possible mechanism underlying cell proliferation, migration and invasion, an obvious prerequisite for metastasis [48]. The rationale for our focusing on RhoGTPases is based on previous reports indicating that CD44-associated cytoskeletal proteins [51,52] and tumor cell-specific phenotypes are dependent on RhoGTPase signaling events [19][20][21]. Here, we summarize recent findings that shed light on the newly recognized RhoGTPase signaling events mediated by HA-CD44 interaction in tumor cells and cancer progression.…”

CD44 Interaction with c-Src Kinase Promotes Cortactin-mediated Cytoskeleton Function and Hyaluronic Acid-dependent Ovarian Tumor Cell Migration

“…In particular, a 15-amino acid sequence located in the cytoplasmic domain of CD44 appears to be required for high affinity ankyrin binding (19 -21). Several factors, including protein kinase C (46,47) and Rho kinase-mediated phosphorylation (17), palmitoylation (48), and GTP binding (49), are required for the up-regulation of CD44-ankyrin interaction. Furthermore, we have found that the S2 subdomain (but not other subdomains) of the ankyrin repeat domain binds to CD44 directly (9); and overexpression of the S2 subdomain of ankyrin repeat domain promotes CD44-mediated human ovarian tumor cell migration (9).…”