Search results for CLIP1

Showing 15 results out of 15

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Protein (3 results from a total of 3)

Identifier: R-HSA-377732
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: CLIP1: P30622
Identifier: R-HSA-9842572
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: CLIP1: P30622
Identifier: R-HSA-9842573
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: CLIP1: P30622

Interactor (1 results from a total of 1)

Identifier: P30622-1
Species: Homo sapiens
Primary external reference: UniProt: P30622-1

Reaction (5 results from a total of 5)

Identifier: R-HSA-5672329
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Once bound to activated RAC1 (RAC1:GTP) or CDC42 (CDC42:GTP), IQGAP1 binds CLIP1 (CLIP-170) via the C-terminus of IQGAP1 and the N-terminus of CLIP1. CLIP1 simultaneously interacts with IQGAP1 and the positive end of microtubules. Formation of the RAC1 or CDC42 complex with IQGAP1, CLIP1 and microtubules determines the orientation of microtubules and results in a polarized cellular morphology (Fukata et al. 2002). The RAC1:GTP:IQGAP1:CLIP1 complex is also involved in the regulation of lamellipodia formation and cell invasion in human breast cancer cells (Suzuki and Takahashi 2008).
Identifier: R-HSA-9842667
Species: Homo sapiens
Compartment: plasma membrane
After dimerization, CLIP1(1-1083)-LTK(488-864) autophosphorylates (Izumi et al, 2021).
Identifier: R-HSA-9845033
Species: Homo sapiens
Compartment: cytosol
The CLIP1-LTK fusion promotes phosphorylation of MAPK1 and MAPK3 (ERK1 and ERK2) as assessed by Western blot (Izumi et al, 2021). The mechanism by which the signal is transmitted from the activated receptor to induce MAPK phosphorylation has not yet been elucidated.
Identifier: R-HSA-9845032
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Activated CLIP1-LTK promotes phosphorylation of AKT at serine 473 as assessed by Western blot (Izumi et al, 2021), although recruitment of PI3K to the activated receptor has not been directly demonstrated.
Identifier: R-HSA-9842659
Species: Homo sapiens
Compartment: plasma membrane
A fusion of CLIP1 and LTK has been identified in a small number of non-small cell lung cancer cases (Izumi et al, 2023). The fusion links the coiled-coil dimerization region of CLIP1 with the intracellular kinase domain of LTK. The fusion protein is constitutively active and supports phosphorylation of MAPK and AKT as well as cellular transformation. CLIP1-LTK-positive cells are sensitive to the ALK inhibitor lorlatinib (Izumi et al, 2021).

Complex (4 results from a total of 4)

Identifier: R-HSA-5672333
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9842602
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9842603
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9845029
Species: Homo sapiens
Compartment: plasma membrane

Pathway (2 results from a total of 2)

Identifier: R-HSA-9842640
Species: Homo sapiens
LTK is a member of the anaplastic lymphoma kinase (ALK)/LTK subfamily within the insulin receptor superfamily of RTKs. LTK encodes an 864-amino-acid protein consisting of extracellular, transmembrane, and tyrosine kinase domains and a short carboxy terminus. The LTK kinase domain shares 80% identity with ALK (Roll and Reuther, 2012). The biological role of LTK is not well defined under normal physiological conditions, and unlike ALK, a clear role for LTK in cancer is also not yet well established. LTK is overexpressed in leukemia, and high expression of LTK in early-stage non-small cell lung cancer (NSCLC) has been associated with greater risk of metastasis (Mueller-Tidow et al, 2005; Roll and Reuther, 2012). More recently, a novel CLIP1-LTK fusion protein has been identified in a small proportion of NSCLC cases (Izumi et al, 2021).
Identifier: R-HSA-9842663
Species: Homo sapiens
Leukocyte tyrosine kinase (LTK) is a transmembrane receptor tyrosine kinase that is a member of the insulin growth factor receptor superfamily. LTK is most closely related to the ALK receptor, and may have originated as a result of a duplication event of the ALK gene (Krowelski and Dalla-Favera, 1991; Dornburg et al, 2021). The extracellular domains of ALK and LTK are characterized by a membrane proximal EGF-like (EGFL) module, a unique 250 amino acid glycine rich (GR) domain that, in Drosophila, is essential for function (Englund et al, 2003), as well as a TNF-like (TNFL) module. The ALK ECD additionally contains two MAM domains, an LDLa domain and a heparin-binding domain (HBD) that are not present in the LTK receptor (Iwahara et al, 1997; Morris et al, 1997; DeMunck et al, 2021). These differences in ECD may contribute to differences in the ligand binding affinities of the two receptors.
LTK is activated by the binding of cytokines ALKAL1 and ALKAL2 to the ECD (Zhang et al, 2014; Reshetnyak et al, 2015; Reshetnyak et al, 2018). Ligand binding induces trans-autophosphorylation in the intracellular domain of the receptor and promotes the interaction and activation of downstream signaling molecules such as SHC, IRS1, CBL and PI3K with the phosphorylated receptor (Kozutsumi et al, 1994; Honda et al, 1994; Ueno et al, 1995; Ueno et al, 1996; Ueno et al, 1997; Li et al, 2004; Yamada et al, 2008). Note however that much of the early functional studies on LTK were conducted before the identification of ALKAL1 and 2 as physiological ligands. In consequence, many of these studies were carried out using chimeric receptors consisting of the ECD (and stimulating ligands) of well-characterized receptors fused to the intracellular domain of LTK.
The exact role of LTK signaling is likewise not fully elucidated. Expression of the chimeric LTK proteins described above promotes neurite outgrowth and cell survival (Ueno et al, 1997; Yamada et al, 2008). A role for LTK in the regulation of transport from the ER to the Golgi has also been proposed, and one study suggests that LTK may actually bean ER-resident protein (Farhan et al, 2010; Centonze et al, 2019). More recently, fusions of LTK have been identified in non-small cell lung cancer (Izumi et al, 2021).
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